Publications by year
In Press
Bezares-Calderón LA, Shahidi R, Jékely G (In Press). A ciliary photoreceptor-cell circuit mediates pressure response in marine zooplankton.
Abstract:
A ciliary photoreceptor-cell circuit mediates pressure response in marine zooplankton
AbstractHydrostatic pressure is a dominant environmental cue for vertically migrating marine organisms but the physiological mechanisms of responding to pressure changes remain unclear. Here we uncovered the cellular and circuit bases of a barokinetic response in the planktonic larva of the marine annelidPlatynereis dumerilii. Increases in pressure induced a rapid, graded and adapting upward swimming response due to faster ciliary beating. By calcium imaging, we found that brain ciliary photoreceptors showed a graded response to pressure changes. The photoreceptors in animals mutant forciliary opsin-1had a smaller ciliary compartment and mutant larvae showed diminished pressure responses. The ciliary photoreceptors synaptically connect to the head multiciliary band that propels swimming via serotonergic motoneurons. Genetic inhibition of the serotonergic cells blocked pressure-dependent increases in ciliary beating. We conclude that ciliary photoreceptors function as pressure sensors and activate ciliary beating through serotonergic signalling during barokinesis.
Abstract.
Thiel D, Bauknecht P, Jékely G, Hejnol A (In Press). A nemertean excitatory peptide/CCHamide regulates ciliary swimming in the larvae of <i>Lineus longissimus</i>.
Abstract:
A nemertean excitatory peptide/CCHamide regulates ciliary swimming in the larvae of Lineus longissimus
AbstractBackgroundThe trochozoan excitatory peptide (EP) and its ortholog, the arthropod CCHamide, are neuropeptides that are only investigated in very few animal species. Previous studies on different trochozoan species focused on their physiological effect in adult specimens, demonstrating a myo-excitatory effect, often on tissues of the digestive system. The function of EP in the planktonic larvae of trochozoans has not yet been studied.ResultsWe surveyed transcriptomes from species of various spiralian (Orthonectia, Nemertea, Brachiopoda, Entoprocta, Rotifera) and ecdysozoan taxa (Tardigrada, Onychophora, Priapulida, Loricifera, Nematomorpha) to investigate the evolution of EPs/CCHamides in protostomes. We found that the EPs of several pilidiophoran nemerteans show a characteristic difference in their C-terminus. Deorphanization of a pilidiophoran EP receptor showed, that the two isoforms of the nemertean Lineus longissimus EP activate a single receptor. We investigated the expression of EP in L. longissimus larvae and juveniles with customized antibodies and found that EP-positive nerves in larvae project from the apical organ to the ciliary band and that EP is expressed more broadly in juveniles in the neuropil and the prominent longitudinal nerve cords. While exposing juvenile L. longissimus specimens to synthetic excitatory peptides did not show any obvious effect, exposure of larvae to either of the two EPs increased the beat frequency of their locomotory cilia and shifted their vertical swimming distribution in a water column upwards.ConclusionOur results show that EP/CCHamide peptides are broadly conserved in protostomes. We show that the EP increases the ciliary beat frequency of L. longissimus larvae, which shifts their vertical distribution in a water column upwards. Endogenous EP may be released at the ciliary band from the projections of apical organ EP-positive neurons to regulate ciliary beating. A locomotory function of EP in L. longissimus larvae, compared to the association of EP/CCHamides with the digestive system in other animals suggests a dynamic integration of orthologous neuropeptides into different functions during evolution.
Abstract.
(In Press). Abstract.
Thiel D, Bauknecht P, Jékely G, Hejnol A (In Press). An ancient FMRFamide-related peptide-receptor pair induces defense behavior in a brachiopod larva.
Abstract:
An ancient FMRFamide-related peptide-receptor pair induces defense behavior in a brachiopod larva
AbstractAnimals show different behaviors that can consist of various spatially or temporally separated sub-reactions. Even less complex organisms, like ciliated larvae that display important behaviors (e.g. metamorphosis, defense, feeding), need to coordinate coherent sub-reactions with their simple nervous system. These behaviors can be triggered by neuropeptides, which are short signaling peptides. Despite the high diversity of neuropeptides in animals, and although their immunoreactivity is widely used in morphological studies of animal nervous systems (e.g. FMRFamide), their function and role in trochozoan larval behavior has so far only been tested in a few cases. When mechanically disturbed, the planktonic larvae of the brachiopodTerebratalia transversaprotrude their stiff and pointy chaetae in a defensive manner and sink down slowly: a startle reaction that is known from different chaetous trochozoan larvae. We found that both of these reactions can be induced simultaneously by the FMRFamide-related neuropeptide FLRFamide. We deorphanized theTerebrataliaFLRFamide receptor and found its expression spatially separated in the apical lobe at the prototroch of the larvae and in the trunk musculature, which correlates with the tissues that are responsible to perform the two sub-reactions. A behavioral assay showed a decreasing efficiency of modified peptides in triggering this behavior, which correlates with the decreasing efficiency of activating the FLRFamide receptor in transfected CHO-K1 cells. Immunohistochemistry andin situhybridization show FLRFamidergic neurons in the apical lobe as well as next to the trunk musculature. Our results show that the single neuropeptide FLRFamide can specifically induce the two coherent sub-reactions of theT. transversastartle behavior.
Abstract.
Bauknecht P, Jékely G (In Press). Ancient coexistence of norepinephrine, tyramine, and octopamine signaling in bilaterians.
Abstract:
Ancient coexistence of norepinephrine, tyramine, and octopamine signaling in bilaterians
AbstractNorepinephrine/noradrenaline is a neurotransmitter implicated in arousal and other aspects of vertebrate behavior and physiology. In invertebrates, adrenergic signaling is considered absent and analogous functions are performed by the biogenic amines octopamine and its precursor tyramine. These chemically similar transmitters signal by related families of GPCR in vertebrates and invertebrates, suggesting that octopamine/tyramine are the invertebrate equivalents of vertebrate norepinephrine. However, the evolutionary relationships and origin of these transmitter systems remain unclear. Using phylogenetic analysis and receptor pharmacology, here we establish that norepinephrine, octopamine, and tyramine receptors coexist in some marine invertebrates. In the protostomesPlatynereis dumerilii(an annelid) andPriapulus caudatus(a priapulid) we identified and pharmacologically characterized adrenergic α1 and α2 receptors that coexist with octopamine α, octopamine β, tyramine type 1, and tyramine 2 receptors. These receptors represent the first examples of adrenergic receptors in protostomes. In the deuterostomeSaccoglossus kowalewskii(a hemichordate), we identified and characterized octopamine α, octopamine β, tyramine type 1, and tyramine 2 receptors, representing the first example of these receptors in deuterostomes.S. kowalewskiialso has adrenergic α1 and α2 receptors, indicating that all three signaling systems coexist in this animal. In phylogenetic analysis, we also identified adrenergic and tyramine receptor orthologs in xenacoelomorphs. Our results clarify the history of monoamine signaling in bilaterians. Since all six receptor families (two each for octopamine and tyramine and three for norepinephrine) can be found in representatives of the two major clades of Bilateria, the protostomes and the deuterostomes, all six receptors coexisted in the protostome-deuterostome last common ancestor. Adrenergic receptors were lost from most insects and nematodes and tyramine and octopamine receptors were lost from most deuterostomes. This complex scenario of differential losses cautions that octopamine signaling in protostomes is not a good model for adrenergic signaling in deuterostomes, and that the studies of marine animals where all three transmitter systems coexist will be needed for a better understanding of the origin and ancestral functions of these transmitters.
Abstract.
Jasek S, Verasztó C, Brodrick E, Shahidi R, Kazimiers T, Kerbl A, Jékely G (In Press). Desmosomal connectomics of all somatic muscles in an annelid larva.
Abstract:
Desmosomal connectomics of all somatic muscles in an annelid larva
AbstractCells form networks in animal tissues through synaptic, chemical and adhesive links. Invertebrate muscle cells often connect to other cells through desmosomes, adhesive junctions anchored by intermediate filaments. To study desmosomal networks, we skeletonised 853 muscle cells and their desmosomal partners in volume electron microscopy data covering an entire larva of the annelidPlatynereis. Muscle cells adhere to each other, to epithelial, glial, ciliated, and bristle-producing cells and to the basal lamina, forming a desmosomal connectome of over 2,000 cells. The aciculae – chitin rods that form an endoskeleton in the segmental appendages – are highly connected hubs in this network. This agrees with the many degrees of freedom of their movement, as revealed by video microscopy. Mapping motoneuron synapses to the desmosomal connectome allowed us to infer the extent of tissue influenced by motoneurons. Our work shows how cellular-level maps of synaptic and adherent force networks can elucidate body mechanics.
Abstract.
Bernardo-Garcia FJ, Syed M, Jékely G, Sprecher SG (In Press). Glass confers rhabdomeric photoreceptor identity in<i>Drosophila</i>, but not across all metazoans.
Abstract:
Glass confers rhabdomeric photoreceptor identity inDrosophila, but not across all metazoans
ABSTRACTAcross metazoans, visual systems employ different types of photoreceptor neurons to detect light. These include rhabdomeric PRs, which exist in distantly related phyla and possess an evolutionarily conserved phototransduction cascade. While the development of rhabdomeric PRs has been thoroughly studied in the fruit flyDrosophila melanogaster, we still know very little about how they form in other species. To investigate this question, we tested whether the transcription factor Glass, which is crucial for instructing rhabdomeric PR formation inDrosophila, may play a similar role in other metazoans. Glass homologues exist throughout the animal kingdom, indicating that this protein evolved prior to the metazoan radiation. Interestingly, our work indicates thatglassis not expressed in rhabdomeric photoreceptors in the planarianSchmidtea mediterraneanor in the annelidPlatynereis dumerilii. Combined with a comparative analysis of the Glass DNA-binding domain, our data suggest that the fate of rhabdomeric PRs is controlled by Glass-dependent and Glass-independent mechanisms in different animal clades.
Abstract.
Varoqueaux F, Williams EA, Grandemange S, Truscello L, Kamm K, Schierwater B, Jékely G, Fasshauer D (In Press). High cell diversity and complex peptidergic signalling underlie placozoan behaviour.
Abstract:
High cell diversity and complex peptidergic signalling underlie placozoan behaviour
SUMMARYPlacozoans, together with sponges, are the only animals devoid of a nervous system and muscles, yet both respond to sensory stimulation in a coordinated manner. How behavioural control in these free-living animals is achieved in the absence of neurons and, more fundamentally, how the first neurons evolved from more primitive communication cells during the rise of animals is not yet understood [1–5]. The placozoan Trichoplax adhaerens is a millimeter-wide, flat, free-living marine animal composed of six morphologically identified cell types distributed across a simple bodyplan [6–9]: a flat upper epithelium and a cylindrical lower epithelium interspersed with a loose layer of fiber cells. Its genome encodes several proneuropeptide genes and genes involved in neurosecretion in animals with a nervous system [10–12]. Here we investigate neuropeptide signalling in Trichoplax adhaerens. We found specific expression of several neuropeptides in non-overlapping cell populations distributed over the three cell layers, revealing an unsuspected cell-type diversity of Trichoplax adhaerens. Using live imaging, we uncovered that treatments with 11 different neuropeptides elicited striking and consistent effects on the animals’ shape, patterns of movement and velocity that we categorized under three main types: (i) crinkling, (ii) turning, and (iii) flattening and churning. Together, the data demonstrate a crucial role for peptidergic signalling in nerveless placozoans and suggest that peptidergic volume signalling may have predated synaptic signalling in the evolution of nervous systems.
Abstract.
Thiel D, Yañez-Guerra LA, Kieswetter A, Cole AG, Temmerman L, Technau U, Jékely G (In Press). Large-scale deorphanization of<i>Nematostella vectensis</i>neuropeptide GPCRs supports the independent expansion of bilaterian and cnidarian peptidergic systems.
Abstract:
Large-scale deorphanization ofNematostella vectensisneuropeptide GPCRs supports the independent expansion of bilaterian and cnidarian peptidergic systems
AbstractNeuropeptides are ancient signaling molecules in animals but only few peptide receptors are known outside bilaterians. Cnidarians possess a large number of G protein-coupled receptors (GPCRs) – the most common receptors of bilaterian neuropeptides – but most of these remain orphan with no known ligands. We searched for neuropeptides in the sea anemoneNematostella vectensisand created a library of 64 peptides derived from 33 precursors. In a large-scale pharmacological screen with these peptides and 161N. vectensisGPCRs, we identified 31 receptors specifically activated by one of 14 peptides. Mapping GPCR and neuropeptide expression to single-cell sequencing data revealed how cnidarian tissues are extensively wired by multilayer peptidergic networks. Phylogenetic analysis identified no direct orthology to bilaterian peptidergic systems and supports the independent expansion of neuropeptide signaling in cnidarians from a few ancestral peptide-receptor pairs.
Abstract.
Thiel D, Yañez Guerra LA, Franz-Wachtel M, Hejnol A, Jékely G (In Press). Nemertean, brachiopod and phoronid neuropeptidomics reveals ancestral spiralian signalling systems.
Abstract:
Nemertean, brachiopod and phoronid neuropeptidomics reveals ancestral spiralian signalling systems
AbstractNeuropeptides are diverse signalling molecules in animals commonly acting through G-protein coupled receptors (GPCRs). Neuropeptides and their receptors underwent extensive diversification in bilaterians and the relationships of many peptide-receptor systems have been clarified. However, we lack a detailed picture of neuropeptide evolution in lophotrochozoans as in-depth studies only exist for molluscs and annelids. Here we analyse peptidergic systems in Nemertea, Brachiopoda and Phoronida. We screened transcriptomes from thirteen nemertean, six brachiopod and four phoronid species for proneuropeptides and neuropeptide GPCRs. With mass spectrometry from the nemerteanLineus longissimus, we validated several predicted peptides and identified novel ones. Molecular phylogeny combined with peptide-sequence and gene-structure comparisons allowed us to comprehensively map spiralian neuropeptide evolution. We found most mollusc and annelid peptidergic systems also in nemerteans, brachiopods and phoronids. We uncovered previously hidden relationships including the orthologies of spiralian CCWamides to arthropod agatoxin-like peptides and of mollusc APGWamides to RGWamides from annelids, with orthologues systems in nemerteans, brachiopods and phoronids. We found that pleurin neuropeptides previously only found in molluscs are also present in nemerteans and brachiopods. We also identified cases of gene family duplications and losses. These include a protostome-specific expansion of RFamide/Wamide signalling, a spiralian expansion of GnRH-related peptides, and duplications of vasopressin/oxytocin before the divergence of brachiopods, phoronids and nemerteans. This analysis expands our knowledge of peptidergic signalling in spiralians and protostomes. Our annotated dataset of nearly 1,300 proneuropeptide sequences and 600 GPCRs presents a useful resource for further studies of neuropeptide signalling in protostomes.
Abstract.
Wan K, Jékely G (In Press). Origins of eukaryotic excitability. Philosophical Transactions of the Royal Society B: Biological Sciences
Luis Alfonso Y-G, Daniel T, Gáspár J (In Press). Pre-metazoan origin of neuropeptide signalling.
Abstract:
Pre-metazoan origin of neuropeptide signalling
AbstractNeuropeptides are a diverse class of signalling molecules in metazoans. They occur in all animals with a nervous system and also in neuron-less placozoans. However, their origin has remained unclear because no neuropeptide shows deep homology across lineages and none have been found in sponges. Here, we identify two neuropeptide precursors, phoenixin and nesfatin, with broad evolutionary conservation. By database searches, sequence alignments and gene-structure comparisons we show that both precursors are present in bilaterians, cnidarians, ctenophores and sponges. We also found phoenixin and a secreted nesfatin precursor homolog in the choanoflagellate Salpingoeca rosetta. Phoenixin in particular, is highly conserved, including its cleavage sites, suggesting that prohormone processing occurs also in choanoflagellates. In addition, based on phyletic patterns and negative pharmacological assays we question the originally proposed GPR-173 (SREB3) as a phoenixin receptor. Our findings indicate that signalling by secreted neuropeptide homologs has pre-metazoan origins and thus evolved before neurons.
Abstract.
Jékely G, Godfrey-Smith P, Keijzer F (In Press). Reafference and the origin of the self in early nervous system evolution.
Abstract:
Reafference and the origin of the self in early nervous system evolution
Discussions of the function of early nervous systems usually focus on a causal flow from sensors to effectors, by which an animal coordinates its actions with exogenous changes in its environment. We propose, instead, that much early sensing was reafferent; it was responsive to the consequences of the animal's own actions. We distinguish two general categories of reafference – translocational and deformational – and use these to survey the distribution of several often-neglected forms of sensing, including gravity sensing, flow sensing, and proprioception. We discuss sensing of these kinds in sponges, ctenophores, placozoans, cnidarians and bilaterians. Reafference is ubiquitous, as ongoing action, especially whole-body motility, will almost inevitably influence the senses. Corollary discharge – a pathway or circuit by which an animal tracks its own actions and their reafferent consequences – is not a necessary feature of reafferent sensing but a later- evolving mechanism. We also argue for the importance of reafferent sensing to the evolution of the body-self, a form of organization that enables an animal to sense and act as a single unit.
Abstract.
Piovani L, Leite DJ, Yañez Guerra LA, Simpson F, Musser JM, Salvador-Martínez I, Marlétaz F, Jékely G, Telford MJ (In Press). Single-cell atlases of two lophotrochozoan larvae highlight their complex evolutionary histories.
Abstract:
Single-cell atlases of two lophotrochozoan larvae highlight their complex evolutionary histories
AbstractPelagic larval stages are widespread across animals, yet it is unclear if larvae were present in the last common ancestor of animals or whether they evolved multiple times due to common selective pressures. Many marine larvae are at least superficially similar, they are small, swim through beating of ciliated bands and sense the environment with an apical organ structure. To understand these similarities, we have generated single cell atlases for marine larvae from two animal phyla and have compared their cell types. We found clear similarities among ciliary band cells and neurons of the apical organ in the two larvae pointing to possible homology of these structures suggesting a single origin of larvae within the clade analysed here (Lophotrochozoa). We also find several clade specific innovations in each larva, including distinct myocytes and shell gland cells in the oyster larva. Oyster shell gland cells express many novel genes which have made previous gene age estimates for trochophore larvae too young.
Abstract.
Jékely G (In Press). The chemical brain hypothesis for the origin of nervous systems.
Abstract:
The chemical brain hypothesis for the origin of nervous systems
In nervous systems, there are two modes of transmission for the propagation of activity between cells. Synaptic transmission relies on close contact at chemical or electrical synapses while volume transmission is mediated by diffusible chemical signals and does not require direct contact. It is possible to wire complex neuronal networks by both chemical and synaptic transmission. Both types of networks are ubiquitous in nervous systems, leading to the question which of the two appeared first in evolution. This paper explores a scenario where chemically organised cellular networks appeared before synapses in evolution; a possibility supported by the presence of complex peptidergic signalling in all animals except sponges. Small peptides are ideally suited to link up cells into chemical networks. They have unlimited diversity, high diffusivity and high copy numbers derived from repetitive precursors. But chemical signalling is diffusion limited and becomes inefficient in larger bodies. To overcome this, peptidergic cells may have developed projections and formed synaptically connected networks tiling body surfaces and displaying synchronised activity with pulsatile peptide release. The advent of circulatory systems and neurohemal organs further reduced the constraint imposed on chemical signalling by diffusion. This could have contributed to the explosive radiation of peptidergic signalling systems in stem bilaterians. Neurosecretory centres in extant nervous systems are still predominantly chemically wired and coexist with the synaptic brain.
Abstract.
Chartier TF, Deschamps J, Duerichen W, Jekely G, Arendt D (In Press). Whole-head recording of chemosensory activity in the marine annelid<i>Platynereis dumerilii</i>.
Abstract:
Whole-head recording of chemosensory activity in the marine annelidPlatynereis dumerilii
Chemical detection is key to various behaviours in both marine and terrestrial animals. Marine species, though highly diverse, have been underrepresented so far in studies on chemosensory systems, and our knowledge mostly concerns the detection of airborne cues. A broader comparative approach is therefore desirable. Marine annelid worms with their rich behavioural repertoire represent attractive models for chemosensory studies. Here, we study the marine wormPlatynereis dumeriliito provide the first comprehensive study of head chemosensory organ physiology in an annelid. By combining microfluidics and calcium imaging, we record neuronal activity in the entire head of early juveniles upon chemical stimulation. We find thatPlatynereisuses four types of organs to detect stimuli such as alcohols, esters, amino acids and sugars. Antennae, but not nuchal organs or palps as generally hypothesised in annelids, are the main chemosensory organs. We report chemically-evoked activity in possible downstream brain regions including the mushroom bodies, which are anatomically and molecularly similar to insect mushroom bodies. We conclude that chemosensation is a major sensory modality for marine annelids, and propose earlyPlatynereisjuveniles as a model to study annelid chemosensory systems.
Abstract.
2023
Moggioli G, Panossian B, Sun Y, Thiel D, Martín-Zamora FM, Tran M, Clifford AM, Goffredi SK, Rimskaya-Korsakova N, Jékely G, et al (2023). Distinct genomic routes underlie transitions to specialised symbiotic lifestyles in deep-sea annelid worms.
Nature Communications,
14(1).
Abstract:
Distinct genomic routes underlie transitions to specialised symbiotic lifestyles in deep-sea annelid worms
AbstractBacterial symbioses allow annelids to colonise extreme ecological niches, such as hydrothermal vents and whale falls. Yet, the genetic principles sustaining these symbioses remain unclear. Here, we show that different genomic adaptations underpin the symbioses of phylogenetically related annelids with distinct nutritional strategies. Genome compaction and extensive gene losses distinguish the heterotrophic symbiosis of the bone-eating worm Osedax frankpressi from the chemoautotrophic symbiosis of deep-sea Vestimentifera. Osedax’s endosymbionts complement many of the host’s metabolic deficiencies, including the loss of pathways to recycle nitrogen and synthesise some amino acids. Osedax’s endosymbionts possess the glyoxylate cycle, which could allow more efficient catabolism of bone-derived nutrients and the production of carbohydrates from fatty acids. Unlike in most Vestimentifera, innate immunity genes are reduced in O. frankpressi, which, however, has an expansion of matrix metalloproteases to digest collagen. Our study supports that distinct nutritional interactions influence host genome evolution differently in highly specialised symbioses.
Abstract.
Benvenuto G, Leone S, Astoricchio E, Bormke S, Jasek S, D’Aniello E, Kittelmann M, McDonald K, Hartenstein V, Baena V, et al (2023). Evolution of the ribbon-like organization of the Golgi apparatus in animal cells.
Jokura K, Ueda N, Gühmann M, Yañez-Guerra LA, Słowiński P, Wedgwood K, Jékely G (2023). Nitric oxide feedback to ciliary photoreceptor cells gates a UV avoidance circuit.
Abstract:
Nitric oxide feedback to ciliary photoreceptor cells gates a UV avoidance circuit
Nitric oxide (NO) produced by nitric-oxide synthase (NOS) is a key regulator of animal physiology. Here we uncover a function for NO in the integration of UV exposure and the gating of a UV-avoidance circuit. We studied UV/violet avoidance mediated by brain ciliary photoreceptors (cPRCs) in larvae of the annelid Platynereis dumerilii. In the larva, NOS is expressed in interneurons (INNOS) postsynaptic to cPRCs. UV stimulation of cPRCs triggers INNOS activation and NO production. NO signals retrogradely to cPRCs to induce their sustained post-stimulus activation through an unconventional guanylate cyclase. This late activation inhibits serotonergic ciliomotor neurons to induce downward swimming. In NOS mutants, retrograde signalling, circuit output and UV avoidance are defective. By mathematical modelling, we recapitulate phototransduction and circuit dynamics in wild-type and mutant larvae. Our results reveal how NO-mediated retrograde signalling gates a synaptic circuit and induces short-term memory of UV exposure to orchestrate light-avoidance behaviour.
Abstract.
Brodrick E, Jékely G (2023). Photobehaviours guided by simple photoreceptor systems.
Animal CognitionAbstract:
Photobehaviours guided by simple photoreceptor systems
AbstractLight provides a widely abundant energy source and valuable sensory cue in nature. Most animals exposed to light have photoreceptor cells and in addition to eyes, there are many extraocular strategies for light sensing. Here, we review how these simpler forms of detecting light can mediate rapid behavioural responses in animals. Examples of these behaviours include photophobic (light avoidance) or scotophobic (shadow) responses, photokinesis, phototaxis and wavelength discrimination. We review the cells and response mechanisms in these forms of elementary light detection, focusing on aquatic invertebrates with some protist and terrestrial examples to illustrate the general principles. Light cues can be used very efficiently by these simple photosensitive systems to effectively guide animal behaviours without investment in complex and energetically expensive visual structures.
Abstract.
Piovani L, Leite DJ, Yañez Guerra LA, Simpson F, Musser JM, Salvador-Martínez I, Marlétaz F, Jékely G, Telford MJ (2023). Single-cell atlases of two lophotrochozoan larvae highlight their complex evolutionary histories.
Science Advances,
9(31).
Abstract:
Single-cell atlases of two lophotrochozoan larvae highlight their complex evolutionary histories
Pelagic larval stages are widespread across animals, yet it is unclear whether larvae were present in the last common ancestor of animals or whether they evolved multiple times due to common selective pressures. Many marine larvae are at least superficially similar; they are small, swim through the beating of bands of cilia, and sense the environment with an apical organ. To understand these similarities, we have generated single-cell atlases for marine larvae from two animal phyla and have compared their cell types. We found clear similarities among ciliary band cells and between neurons of the apical organ in the two larvae pointing to possible homology of these structures, suggesting a single origin of larvae within Spiralia. We also find several clade-specific innovations in each larva, including distinct myocytes and shell gland cells in the oyster larva. Oyster shell gland cells express many recently evolved genes that have made previous gene age estimates for the origin of trochophore larvae too young.
Abstract.
2022
Jasek S, Verasztó C, Brodrick E, Shahidi R, Kazimiers T, Kerbl A, Jékely G (2022). Desmosomal connectomics of all somatic muscles in an annelid larva.
eLife,
11Abstract:
Desmosomal connectomics of all somatic muscles in an annelid larva
Cells form networks in animal tissues through synaptic, chemical, and adhesive links. Invertebrate muscle cells often connect to other cells through desmosomes, adhesive junctions anchored by intermediate filaments. To study desmosomal networks, we skeletonised 853 muscle cells and their desmosomal partners in volume electron microscopy data covering an entire larva of the annelid Platynereis. Muscle cells adhere to each other, to epithelial, glial, ciliated, and bristle-producing cells and to the basal lamina, forming a desmosomal connectome of over 2000 cells. The aciculae – chitin rods that form an endoskeleton in the segmental appendages – are highly connected hubs in this network. This agrees with the many degrees of freedom of their movement, as revealed by video microscopy. Mapping motoneuron synapses to the desmosomal connectome allowed us to infer the extent of tissue influenced by motoneurons. Our work shows how cellular-level maps of synaptic and adherent force networks can elucidate body mechanics.
Abstract.
Martín-Durán J, Moggioli G, Panossian B, Sun Y, Thiel D, Martin-Zamora F, Tran M, Clifford A, Goffredi S, Rimskaya-Korsakova N, et al (2022). Distinct genomic routes underlie transitions to specialised symbiotic lifestyles in deep sea annelid worms.
Yañez-Guerra LA, Thiel D, Jékely G (2022). Premetazoan Origin of Neuropeptide Signaling.
Molecular Biology and Evolution,
39(4).
Abstract:
Premetazoan Origin of Neuropeptide Signaling
Abstract
. Neuropeptides are a diverse class of signaling molecules in metazoans. They occur in all animals with a nervous system and also in neuron-less placozoans. However, their origin has remained unclear because no neuropeptide shows deep homology across lineages, and none have been found in sponges. Here, we identify two neuropeptide precursors, phoenixin (PNX) and nesfatin, with broad evolutionary conservation. By database searches, sequence alignments, and gene-structure comparisons, we show that both precursors are present in bilaterians, cnidarians, ctenophores, and sponges. We also found PNX and a secreted nesfatin precursor homolog in the choanoflagellate Salpingoeca rosetta. PNX, in particular, is highly conserved, including its cleavage sites, suggesting that prohormone processing occurs also in choanoflagellates. In addition, based on phyletic patterns and negative pharmacological assays, we question the originally proposed GPR-173 (SREB3) as a PNX receptor. Our findings revealed that secreted neuropeptide homologs derived from longer precursors have premetazoan origins and thus evolved before neurons.
Abstract.
Moggioli G, Panossian B, Sun Y, Thiel D, Martín-Zamora F, Tran M, Clifford A, Goffredi S, Rimskaya-Korsakova N, Jékelly G, et al (2022). The hologenome of <i>Osedax frankpressi</i> reveals the genetic interplay for the symbiotic digestion of vertebrate bone.
Abstract:
The hologenome of Osedax frankpressi reveals the genetic interplay for the symbiotic digestion of vertebrate bone
The marine annelid Osedax has evolved a unique heterotrophic symbiosis that allows it to feed exclusively on sunken bones. Yet, the genetic and physiological principles sustaining this symbiosis are poorly understood. Here we show that Osedax frankpressi has a small, AT-rich genome shaped by extensive gene loss. While the Oceanospirillales endosymbiont of Osedax is enriched in genes for carbohydrate and nitrogen metabolism, O. frankpressi has undergone genetic changes to accommodate bone digestion, including the expansion of matrix metalloproteases, and a loss of pathways to synthesize amino acids that are abundant in collagen. Unlike other symbioses, however, innate immunity genes required to acquire and control the endosymbionts are reduced in O. frankpressi. These findings reveal Osedax has evolved an alternative genomic toolkit to bacterial symbiosis where host-symbiont co-dependence has favoured genome simplicity in the host to exploit the nutritionally unbalanced diet of bones. Teaser Genome reduction and adaptations for collagen digestion underpin the symbiosis of Osedax worms to exploit decaying bones.
Abstract.
2021
Jékely G, Budd GE (2021). Animal Phylogeny: Resolving the Slugfest of Ctenophores, Sponges and Acoels?.
Current Biology,
31(4), R202-R204.
Abstract:
Animal Phylogeny: Resolving the Slugfest of Ctenophores, Sponges and Acoels?
Animal phylogeny has always been controversial, but a new study brings some much-needed order for two infamous wandering groups, the ctenophores and the Xenacoelomorphs. The study introduces an innovative approach to dissect systematic errors in the underlying methodology of molecular phylogenies. Animal phylogeny has always been controversial, but a new study brings some much-needed order for two infamous wandering groups, the ctenophores and the Xenacoelomorphs. The study introduces an innovative approach to dissect systematic errors in the underlying methodology of molecular phylogenies.
Abstract.
Thiel D, Yañez-Guerra LA, Franz-Wachtel M, Hejnol A, Jékely G (2021). Nemertean, Brachiopod, and Phoronid Neuropeptidomics Reveals Ancestral Spiralian Signaling Systems.
Mol Biol Evol,
38(11), 4847-4866.
Abstract:
Nemertean, Brachiopod, and Phoronid Neuropeptidomics Reveals Ancestral Spiralian Signaling Systems.
Neuropeptides are diverse signaling molecules in animals commonly acting through G-protein coupled receptors (GPCRs). Neuropeptides and their receptors underwent extensive diversification in bilaterians and the relationships of many peptide-receptor systems have been clarified. However, we lack a detailed picture of neuropeptide evolution in lophotrochozoans as in-depth studies only exist for mollusks and annelids. Here, we analyze peptidergic systems in Nemertea, Brachiopoda, and Phoronida. We screened transcriptomes from 13 nemertean, 6 brachiopod, and 4 phoronid species for proneuropeptides and neuropeptide GPCRs. With mass spectrometry from the nemertean Lineus longissimus, we validated several predicted peptides and identified novel ones. Molecular phylogeny combined with peptide-sequence and gene-structure comparisons allowed us to comprehensively map spiralian neuropeptide evolution. We found most mollusk and annelid peptidergic systems also in nemerteans, brachiopods, and phoronids. We uncovered previously hidden relationships including the orthologies of spiralian CCWamides to arthropod agatoxin-like peptides and of mollusk APGWamides to RGWamides from annelids, with ortholog systems in nemerteans, brachiopods, and phoronids. We found that pleurin neuropeptides previously only found in mollusks are also present in nemerteans and brachiopods. We also identified cases of gene family duplications and losses. These include a protostome-specific expansion of RFamide/Wamide signaling, a spiralian expansion of GnRH-related peptides, and duplications of vasopressin/oxytocin before the divergence of brachiopods, phoronids, and nemerteans. This analysis expands our knowledge of peptidergic signaling in spiralians and other protostomes. Our annotated data set of nearly 1,300 proneuropeptide sequences and 600 GPCRs presents a useful resource for further studies of neuropeptide signaling.
Abstract.
Author URL.
Jékely G, Godfrey-Smith P, Keijzer F (2021). Reafference and the origin of the self in early nervous system evolution.
Philos Trans R Soc Lond B Biol Sci,
376(1821).
Abstract:
Reafference and the origin of the self in early nervous system evolution.
Discussions of the function of early nervous systems usually focus on a causal flow from sensors to effectors, by which an animal coordinates its actions with exogenous changes in its environment. We propose, instead, that much early sensing was reafferent; it was responsive to the consequences of the animal's own actions. We distinguish two general categories of reafference-translocational and deformational-and use these to survey the distribution of several often-neglected forms of sensing, including gravity sensing, flow sensing and proprioception. We discuss sensing of these kinds in sponges, ctenophores, placozoans, cnidarians and bilaterians. Reafference is ubiquitous, as ongoing action, especially whole-body motility, will almost inevitably influence the senses. Corollary discharge-a pathway or circuit by which an animal tracks its own actions and their reafferent consequences-is not a necessary feature of reafferent sensing but a later-evolving mechanism. We also argue for the importance of reafferent sensing to the evolution of the body-self, a form of organization that enables an animal to sense and act as a single unit. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.
Abstract.
Author URL.
Özpolat BD, Randel N, Williams EA, Bezares-Calderón LA, Andreatta G, Balavoine G, Bertucci PY, Ferrier DEK, Gambi MC, Gazave E, et al (2021). The Nereid on the rise: Platynereis as a model system.
Evodevo,
12(1).
Abstract:
The Nereid on the rise: Platynereis as a model system.
The Nereid Platynereis dumerilii (Audouin and Milne Edwards (Annales des Sciences Naturelles 1:195-269, 1833) is a marine annelid that belongs to the Nereididae, a family of errant polychaete worms. The Nereid shows a pelago-benthic life cycle: as a general characteristic for the superphylum of Lophotrochozoa/Spiralia, it has spirally cleaving embryos developing into swimming trochophore larvae. The larvae then metamorphose into benthic worms living in self-spun tubes on macroalgae. Platynereis is used as a model for genetics, regeneration, reproduction biology, development, evolution, chronobiology, neurobiology, ecology, ecotoxicology, and most recently also for connectomics and single-cell genomics. Research on the Nereid started with studies on eye development and spiralian embryogenesis in the nineteenth and early twentieth centuries. Transitioning into the molecular era, Platynereis research focused on posterior growth and regeneration, neuroendocrinology, circadian and lunar cycles, fertilization, and oocyte maturation. Other work covered segmentation, photoreceptors and other sensory cells, nephridia, and population dynamics. Most recently, the unique advantages of the Nereid young worm for whole-body volume electron microscopy and single-cell sequencing became apparent, enabling the tracing of all neurons in its rope-ladder-like central nervous system, and the construction of multimodal cellular atlases. Here, we provide an overview of current topics and methodologies for P. dumerilii, with the aim of stimulating further interest into our unique model and expanding the active and vibrant Platynereis community.
Abstract.
Author URL.
Jékely G (2021). The chemical brain hypothesis for the origin of nervous systems.
Philos Trans R Soc Lond B Biol Sci,
376(1821).
Abstract:
The chemical brain hypothesis for the origin of nervous systems.
In nervous systems, there are two main modes of transmission for the propagation of activity between cells. Synaptic transmission relies on close contact at chemical or electrical synapses while volume transmission is mediated by diffusible chemical signals and does not require direct contact. It is possible to wire complex neuronal networks by both chemical and synaptic transmission. Both types of networks are ubiquitous in nervous systems, leading to the question which of the two appeared first in evolution. This paper explores a scenario where chemically organized cellular networks appeared before synapses in evolution, a possibility supported by the presence of complex peptidergic signalling in all animals except sponges. Small peptides are ideally suited to link up cells into chemical networks. They have unlimited diversity, high diffusivity and high copy numbers derived from repetitive precursors. But chemical signalling is diffusion limited and becomes inefficient in larger bodies. To overcome this, peptidergic cells may have developed projections and formed synaptically connected networks tiling body surfaces and displaying synchronized activity with pulsatile peptide release. The advent of circulatory systems and neurohemal organs further reduced the constraint imposed on chemical signalling by diffusion. This could have contributed to the explosive radiation of peptidergic signalling systems in stem bilaterians. Neurosecretory centres in extant nervous systems are still predominantly chemically wired and coexist with the synaptic brain. This article is part of the theme issue 'Basal cognition: multicellularity, neurons and the cognitive lens'.
Abstract.
Author URL.
Benito-Gutiérrez È, Gattoni G, Stemmer M, Rohr SD, Schuhmacher LN, Tang J, Marconi A, Jékely G, Arendt D (2021). The dorsoanterior brain of adult amphioxus shares similarities in expression profile and neuronal composition with the vertebrate telencephalon.
BMC Biol,
19(1).
Abstract:
The dorsoanterior brain of adult amphioxus shares similarities in expression profile and neuronal composition with the vertebrate telencephalon.
BACKGROUND: the evolutionary origin of the telencephalon, the most anterior part of the vertebrate brain, remains obscure. Since no obvious counterpart to the telencephalon has yet been identified in invertebrate chordates, it is difficult to trace telencephalic origins. One way to identify homologous brain parts between distantly related animal groups is to focus on the combinatorial expression of conserved regionalisation genes that specify brain regions. RESULTS: Here, we report the combined expression of conserved transcription factors known to specify the telencephalon in the vertebrates in the chordate amphioxus. Focusing on adult specimens, we detect specific co-expression of these factors in the dorsal part of the anterior brain vesicle, which we refer to as Pars anterodorsalis (PAD). As in vertebrates, expression of the transcription factors FoxG1, Emx and Lhx2/9 overlaps that of Pax4/6 dorsally and of Nkx2.1 ventrally, where we also detect expression of the Hedgehog ligand. This specific pattern of co-expression is not observed prior to metamorphosis. Similar to the vertebrate telencephalon, the amphioxus PAD is characterised by the presence of GABAergic neurons and dorsal accumulations of glutamatergic as well as dopaminergic neurons. We also observe sustained proliferation of neuronal progenitors at the ventricular zone of the amphioxus brain vesicle, as observed in the vertebrate brain. CONCLUSIONS: Our findings suggest that the PAD in the adult amphioxus brain vesicle and the vertebrate telencephalon evolved from the same brain precursor region in ancestral chordates, which would imply homology of these structures. Our comparative data also indicate that this ancestral brain already contained GABA-, glutamatergic and dopaminergic neurons, as is characteristic for the olfactory bulb of the vertebrate telencephalon. We further speculate that the telencephalon might have evolved in vertebrates via a heterochronic shift in developmental timing.
Abstract.
Author URL.
2020
Quiroga Artigas G, Lapébie P, Leclère L, Bauknecht P, Uveira J, Chevalier S, Jékely G, Momose T, Houliston E (2020). A G protein–coupled receptor mediates neuropeptide-induced oocyte maturation in the jellyfish Clytia. PLOS Biology, 18(3), e3000614-e3000614.
Bezares-Calderón LA, Berger J, Jékely G (2020). Diversity of cilia-based mechanosensory systems and their functions in marine animal behaviour.
Philosophical Transactions of the Royal Society B: Biological Sciences,
375(1792).
Abstract:
Diversity of cilia-based mechanosensory systems and their functions in marine animal behaviour
Sensory cells that detect mechanical forces usually have one ormore specialized cilia. These mechanosensory cells underlie hearing, proprioception or gravity sensation. To date, it is unclear how cilia contribute to detecting mechanical forces and what is the relationship between mechanosensory ciliated cells in different animal groups and sensory systems.Here,we reviewexamples of ciliated sensory cells with a focus on marine invertebrate animals. We discuss how various ciliated cells mediate mechanosensory responses during feeding, tactic responses or predator-prey interactions. We also highlight some of these systems as interesting and accessible models for future in-depth behavioural, functional and molecular studies. We envisage that embracing a broader diversity of organisms could lead to a more complete view of cilia-based mechanosensation.
Abstract.
Marinković M, Berger J, Jékely G (2020). Neuronal coordination of motile cilia in locomotion and feeding.
Philosophical Transactions of the Royal Society B: Biological Sciences,
375(1792).
Abstract:
Neuronal coordination of motile cilia in locomotion and feeding
Efficient ciliary locomotion and transport require the coordination of motile cilia. Short-range coordination of ciliary beats can occur by biophysical mechanisms. Long-range coordination across large or disjointed ciliated fields often requires nervous system control and innervation of ciliated cells by ciliomotor neurons. The neuronal control of cilia is best understood in invertebrate ciliated microswimmers, but similar mechanisms may operate in the vertebrate body. Here, we review how the study of aquatic invertebrates contributed to our understanding of the neuronal control of cilia. We summarize the anatomy of ciliomotor systems and the physiological mechanisms that can alter ciliary activity. We also discuss the most well-characterized ciliomotor system, that of the larval annelid Platynereis. Here, pacemaker neurons drive the rhythmic activation of cholinergic and serotonergic ciliomotor neurons to induce ciliary arrests and beating. The Platynereis ciliomotor neurons form a distinct part of the larval nervous system. Similar ciliomotor systems likely operate in other ciliated larvae, such as mollusc veligers. We discuss the possible ancestry and conservation of ciliomotor circuits and highlight how comparative experimental approaches could contribute to a better understanding of the evolution and function of ciliary systems.
Abstract.
Wan KY, Jékely G (2020). On the unity and diversity of cilia.
Philosophical Transactions of the Royal Society B: Biological Sciences,
375(1792).
Abstract:
On the unity and diversity of cilia
Cilia are specialized cellular organelles that are united in structure and implicated in diverse key life processes across eukaryotes. In both unicellular and multicellular organisms, variations on the same ancestral form mediate sensing, locomotion and the production of physiological flows. As we usher in a new, more interdisciplinary era, the way we study cilia is changing. This special theme issue brings together biologists, biophysicists and mathematicians to highlight the remarkable range of systems in which motile cilia fulfil vital functions, and to inspire and define novel strategies for future research.
Abstract.
Corbett A, Gintoli M, Mohanan S, Williams E, Jekely G, Salter PS (2020). Spinning Disk - Remote Focusing Microscopy (data set).
Author URL.
Gintoli M, Mohanan S, Salter P, Williams E, Beard JD, Jekely G, Corbett AD (2020). Spinning Disk -- Remote Focusing Microscopy.
Gintoli M, Mohanan S, Salter P, Williams E, Beard JD, Jekely G, Corbett AD (2020). Spinning disk-remote focusing microscopy.
Biomedical Optics Express,
11(6), 2874-2888.
Abstract:
Spinning disk-remote focusing microscopy
Fast confocal imaging was achieved by combining remote focusing with differential spinning disk optical sectioning to rapidly acquire images of live samples at cellular resolution. Axial and lateral full width half maxima less than 5 μm and 490 nm respectively are demonstrated over 130 μm axial range with a 256 × 128 μm field of view. A water-index calibration slide was used to achieve an alignment that minimises image volume distortion. Application to live biological samples was demonstrated by acquiring image volumes over a 24 μm axial range at 1 volume/s, allowing for the detection of calcium-based neuronal activity in Platynereis dumerilii larvae.
Abstract.
2019
Thiel D, Bauknecht P, Jékely G, Hejnol A (2019). A nemertean excitatory peptide/CCHamide regulates ciliary swimming in the larvae of Lineus longissimus.
Frontiers in Zoology,
16(1).
Abstract:
A nemertean excitatory peptide/CCHamide regulates ciliary swimming in the larvae of Lineus longissimus
Background: the trochozoan excitatory peptide (EP) and its ortholog, the arthropod CCHamide, are neuropeptides that are only investigated in very few animal species. Previous studies on different trochozoan species focused on their physiological effect in adult specimens, demonstrating a myo-excitatory effect, often on tissues of the digestive system. The function of EP in the planktonic larvae of trochozoans has not yet been studied. Results: We surveyed transcriptomes from species of various spiralian (Orthonectida, Nemertea, Brachiopoda, Entoprocta, Rotifera) and ecdysozoan taxa (Tardigrada, Onychophora, Priapulida, Loricifera, Nematomorpha) to investigate the evolution of EPs/CCHamides in protostomes. We found that the EPs of several pilidiophoran nemerteans show a characteristic difference in their C-terminus. Deorphanization of a pilidiophoran EP receptor showed, that the two splice variants of the nemertean Lineus longissimus EP activate a single receptor. We investigated the expression of EP in L. longissimus larvae and juveniles with customized antibodies and found that EP positive nerves in larvae project from the apical organ to the ciliary band and that EP is expressed more broadly in juveniles in the neuropil and the prominent longitudinal nerve cords. While exposing juvenile L. longissimus specimens to synthetic excitatory peptides did not show any obvious effect, exposure of larvae to either of the two EPs increased the beat frequency of their locomotory cilia and shifted their vertical swimming distribution in a water column upwards. Conclusion: Our results show that EP/CCHamide peptides are broadly conserved in protostomes. We show that the EP increases the ciliary beat frequency of L. longissimus larvae, which shifts their vertical distribution in a water column upwards. Endogenous EP may be released at the ciliary band from the projections of apical organ EP positive neurons to regulate ciliary beating. This locomotory function of EP in L. longissimus larvae stands in contrast to the repeated association of EP/CCHamides with its myo-excitatory effect in adult trochozoans and the general association with the digestive system in many protostomes.
Abstract.
Buchholz TO, Krull A, Shahidi R, Pigino G, Jékely G, Jug F (2019). Content-aware image restoration for electron microscopy. In (Ed)
Methods in Cell Biology, 277-289.
Abstract:
Content-aware image restoration for electron microscopy
Abstract.
Jékely G, Arnone MI (2019). Editorial overview: Tissue-level dynamics in development and evolution. Current Opinion in Genetics and Development, 57, iii-v.
Jékely G (2019). Evolution: How Not to Become an Animal.
Current Biology,
29(23), R1240-R1242.
Abstract:
Evolution: How Not to Become an Animal
The origin of animals has always fascinated biologists. Studies on choanoflagellates, the closest living relatives of animals, have contributed major insights. The discovery of a multicellular choanoflagellate with light-regulated collective behaviour now provides a new perspective.
Abstract.
Bernardo-Garcia FJ, Syed M, Jékely G, Sprecher SG (2019). Glass confers rhabdomeric photoreceptor identity in Drosophila, but not across all metazoans.
EvoDevo,
10(1).
Abstract:
Glass confers rhabdomeric photoreceptor identity in Drosophila, but not across all metazoans
Across metazoans, visual systems employ different types of photoreceptor neurons (PRs) to detect light. These include rhabdomeric PRs, which exist in distantly related phyla and possess an evolutionarily conserved phototransduction cascade. While the development of rhabdomeric PRs has been thoroughly studied in the fruit fly Drosophila melanogaster, we still know very little about how they form in other species. To investigate this question, we tested whether the transcription factor Glass, which is crucial for instructing rhabdomeric PR formation in Drosophila, may play a similar role in other metazoans. Glass homologues exist throughout the animal kingdom, indicating that this protein evolved prior to the metazoan radiation. Interestingly, our work indicates that glass is not expressed in rhabdomeric photoreceptors in the planarian Schmidtea mediterranea nor in the annelid Platynereis dumerilii. Combined with a comparative analysis of the Glass DNA-binding domain, our data suggest that the fate of rhabdomeric PRs is controlled by Glass-dependent and Glass-independent mechanisms in different animal clades.
Abstract.
Williams EA, Jékely G (2019). Neuronal cell types in the annelid Platynereis dumerilii.
Current Opinion in Neurobiology,
56, 106-116.
Abstract:
Neuronal cell types in the annelid Platynereis dumerilii
The marine annelid Platynereis dumerilii is an invertebrate laboratory model for developmental biology and neuroscience. Its larval stages are small and transparent, enabling whole-body analyses of cell-type diversity and neuronal circuits. Here, we review the diversity of neuronal cell types in Platynereis. A variety of approaches have been used to identify cell types in Platynereis including whole-body gene expression atlases, single-cell RNA-seq and whole-body connectomics through serial EM reconstruction. The function of several cell types and neuronal circuits has also been analysed with experimental approaches. Platynereis has aspects of biology and cell types that are absent from the major invertebrate model organisms (C. elegans and Drosophila) including ciliary locomotion, noradrenergic neurons and ciliary photoreceptor cells.
Abstract.
2018
Quiroga Artigas G, Lapébie P, Leclère L, Takeda N, Deguchi R, Jékely G, Momose T, Houliston E (2018). A gonad-expressed opsin mediates light-induced spawning in the jellyfish clytia.
eLife,
7Abstract:
A gonad-expressed opsin mediates light-induced spawning in the jellyfish clytia
Across the animal kingdom, environmental light cues are widely involved in regulating gamete release, but the molecular and cellular bases of the photoresponsive mechanisms are poorly understood. In hydrozoan jellyfish, spawning is triggered by dark-light or light-dark transitions acting on the gonad, and is mediated by oocyte maturation-inducing neuropeptide hormones (MIHs) released from the ectoderm. We determined in Clytia hemisphaerica that blue-cyan light triggers spawning in isolated gonads. A candidate opsin (Opsin9) was found co-expressed with MIH within specialised ectodermal cells. Opsin9 knockout jellyfish generated by CRISPR/Cas9 failed to undergo oocyte maturation and spawning, a phenotype reversible by synthetic MIH. Gamete maturation and release in Clytia is thus regulated by gonadal photosensory-neurosecretory cells that secrete MIH in response to light via Opsin9. Similar cells in ancestral eumetazoans may have allowed tissue-level photo-regulation of diverse behaviours, a feature elaborated in cnidarians in parallel with expansion of the opsin gene family.
Abstract.
Verasztó C, Gühmann M, Jia H, Rajan VBV, Bezares-Calderón LA, Piñeiro-Lopez C, Randel N, Shahidi R, Michiels NK, Yokoyama S, et al (2018). Ciliary and rhabdomeric photoreceptor-cell circuits form a spectral depth gauge in marine zooplankton.
eLife,
7Abstract:
Ciliary and rhabdomeric photoreceptor-cell circuits form a spectral depth gauge in marine zooplankton
Ciliary and rhabdomeric photoreceptor cells represent two main lines of photoreceptor-cell evolution in animals. The two cell types coexist in some animals, however how these cells functionally integrate is unknown. We used connectomics to map synaptic paths between ciliary and rhabdomeric photoreceptors in the planktonic larva of the annelid Platynereis and found that ciliary photoreceptors are presynaptic to the rhabdomeric circuit. The behaviors mediated by the ciliary and rhabdomeric cells also interact hierarchically. The ciliary photoreceptors are UV-sensitive and mediate downward swimming in non-directional UV light, a behavior absent in ciliary-opsin knockout larvae. UV avoidance overrides positive phototaxis mediated by the rhabdomeric eyes such that vertical swimming direction is determined by the ratio of blue/UV light. Since this ratio increases with depth, Platynereis larvae may use it as a depth gauge during vertical migration. Our results revealed a functional integration of ciliary and rhabdomeric photoreceptor cells in a zooplankton larva.
Abstract.
Schmidt A, Bauknecht P, Williams EA, Augustinowski K, Gründer S, Jékely G (2018). Dual signaling of Wamide myoinhibitory peptides through a peptide-gated channel and a GPCR in Platynereis.
FASEB J,
32(10), 5338-5349.
Abstract:
Dual signaling of Wamide myoinhibitory peptides through a peptide-gated channel and a GPCR in Platynereis.
Neuropeptides commonly signal by metabotropic GPCRs. In some mollusks and cnidarians, RFamide neuropeptides mediate fast ionotropic signaling by peptide-gated ion channels that belong to the DEG/ENaC family. Here we describe a neuropeptide system with a dual mode of signaling by both a peptide-gated ion channel and a GPCR. We identified and characterized a peptide-gated channel in the marine annelid Platynereis dumerilii that is specifically activated by Wamide myoinhibitory peptides derived from the same proneuropeptide. The myoinhibitory peptide-gated ion channel (MGIC) belongs to the DEG/ENaC family and is paralogous to RFamide-gated ion channels. Platynereis myoinhibitory peptides also activate a previously described GPCR, MAG. We measured the potency of all Wamides on both MGIC and MAG and identified peptides that preferentially activate one or the other receptor. Analysis of a single-cell transcriptome resource indicates that MGIC and MAG signal in distinct target neurons. The identification of a Wamide-gated ion channel suggests that peptide-gated channels are more diverse and widespread in animals than previously appreciated. The possibility of neuropeptide signaling by both ionotropic and metabotropic receptors to different target cells in the same organism highlights an additional level of complexity in peptidergic signaling networks.-Schmidt, A. Bauknecht, P. Williams, E. A. Augustinowski, K. Gründer, S. Jékely, G. Dual signaling of Wamide myoinhibitory peptides through a peptide-gated channel and a GPCR in Platynereis.
Abstract.
Author URL.
Varoqueaux F, Williams EA, Grandemange S, Truscello L, Kamm K, Schierwater B, Jékely G, Fasshauer D (2018). High Cell Diversity and Complex Peptidergic Signaling Underlie Placozoan Behavior.
Curr Biol,
28(21), 3495-3501.e2.
Abstract:
High Cell Diversity and Complex Peptidergic Signaling Underlie Placozoan Behavior.
Placozoans, together with sponges, are the only animals devoid of a nervous system and muscles, yet both respond to sensory stimulation in a coordinated manner. How behavioral control in these free-living animals is achieved in the absence of neurons and, more fundamentally, how the first neurons evolved from more primitive cells for communication during the rise of animals are not yet understood [1-5]. The placozoan Trichoplax adhaerens is a millimeter-wide, flat, free-living marine animal composed of six morphologically identified cell types distributed across a simple body plan [6-9]: a thin upper epithelium and a columnar lower epithelium interspersed with a loose layer of fiber cells in between. Its genome contains genes encoding several neuropeptide-precursor-like proteins and orthologs of proteins involved in neurosecretion in animals with a nervous system [10-12]. Here we investigate peptidergic signaling in T. adhaerens. We found specific expression of several neuropeptide-like molecules in non-overlapping cell populations distributed over the three cell layers, revealing an unsuspected cell-type diversity of T. adhaerens. Using live imaging, we discovered that treatments with 11 different peptides elicited striking and consistent effects on the animals' shape, patterns of movement, and velocity that we categorized under three main types: (1) crinkling, (2) turning, and (3) flattening and churning. Together, the data demonstrate a crucial role for peptidergic signaling in nerveless placozoans and suggest that peptidergic volume signaling may have pre-dated synaptic signaling in the evolution of nervous systems.
Abstract.
Author URL.
Bezares-Calderón LA, Berger J, Jasek S, Verasztó C, Mendes S, Gühmann M, Almeda R, Shahidi R, Jékely G (2018). Neural circuitry of a polycystin-mediated hydrodynamic startle response for predator avoidance.
eLife,
7Abstract:
Neural circuitry of a polycystin-mediated hydrodynamic startle response for predator avoidance
Startle responses triggered by aversive stimuli including predators are widespread across animals. These coordinated whole-body actions require the rapid and simultaneous activation of a large number of muscles. Here we study a startle response in a planktonic larva to understand the whole-body circuit implementation of the behaviour. Upon encountering water vibrations, larvae of the annelid Platynereis close their locomotor cilia and simultaneously raise the parapodia. The response is mediated by collar receptor neurons expressing the polycystins PKD1-1 and PKD2-1. CRISPR-generated PKD1-1 and PKD2-1 mutant larvae do not startle and fall prey to a copepod predator at a higher rate. Reconstruction of the whole-body connectome of the collar-receptor-cell circuitry revealed converging feedforward circuits to the ciliary bands and muscles. The wiring diagram suggests circuit mechanisms for the intersegmental and left-right coordination of the response. Our results reveal how polycystin-mediated mechanosensation can trigger a coordinated whole-body effector response involved in predator avoidance.
Abstract.
Jékely G, Melzer S, Beets I, Kadow ICG, Koene J, Haddad S, Holden-Dye L (2018). The long and the short of it -A perspective on peptidergic regulation of circuits and behaviour.
Journal of Experimental Biology,
221(3).
Abstract:
The long and the short of it -A perspective on peptidergic regulation of circuits and behaviour
Neuropeptides are the most diverse class of chemical modulators in nervous systems. They contribute to extensive modulation of circuit activity and have profound influences on animal physiology. Studies on invertebrate model organisms, including the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans, have enabled the genetic manipulation of peptidergic signalling, contributing to an understanding of how neuropeptides pattern the output of neural circuits to underpin behavioural adaptation. Electrophysiological and pharmacological analyses of well-defined microcircuits, such as the crustacean stomatogastric ganglion, have provided detailed insights into neuropeptide functions at a cellular and circuit level. These approaches can be increasingly applied in the mammalian brain by focusing on circuits with a defined and identifiable sub-population of neurons. Functional analyses of neuropeptide systems have been underpinned by systematic studies to map peptidergic networks. Here, we review the general principles and mechanistic insights that have emerged from these studies. We also highlight some of the challenges that remain for furthering our understanding of the functional relevance of peptidergic modulation.
Abstract.
Chartier TF, Deschamps J, Dürichen W, Jékely G, Arendt D (2018). Whole-head recording of chemosensory activity in the marine annelid Platynereis dumerilii.
Open Biology,
8(10).
Abstract:
Whole-head recording of chemosensory activity in the marine annelid Platynereis dumerilii
Chemical detection is key to various behaviours in both marine and terrestrial animals. Marine species, though highly diverse, have been underrepresented so far in studies on chemosensory systems, and our knowledge mostly concerns the detection of airborne cues. A broader comparative approach is therefore desirable. Marine annelid worms with their rich behavioural repertoire represent attractive models for chemosensation. Here, we study the marine worm Platynereis dumerilii to provide the first comprehensive investigation of head chemosensory organ physiology in an annelid. By combining microfluidics and calcium imaging, we record neuronal activity in the entire head of early juveniles upon chemical stimulation. We find that Platynereis uses four types of organs to detect stimuli such as alcohols, esters, amino acids and sugars. Antennae are the main chemosensory organs, compared to the more differentially responding nuchal organs or palps. We report chemically evoked activity in possible downstream brain regions including the mushroom bodies (MBs), which are anatomically and molecularly similar to insect MBs. We conclude that chemosensation is a major sensory modality for marine annelids and propose early Platynereis juveniles as a model to study annelid chemosensory systems.
Abstract.
2017
Thiel D, Bauknecht P, Jeákely G, Hejnol A (2017). An ancient FMRFamide-related peptide-receptor pair induces defence behaviour in a brachiopod larva.
Open Biology,
7(8).
Abstract:
An ancient FMRFamide-related peptide-receptor pair induces defence behaviour in a brachiopod larva
Animal behaviour often comprises spatially separated sub-reactions and even ciliated larvae are able to coordinate sub-reactions of complex behaviours (metamorphosis, feeding). How these sub-reactions are coordinated is currently not well understood. Neuropeptides are potential candidates for triggering larval behaviour. However, although their immunoreactivity has been widely analysed, their function in trochozoan larvae has only been studied for a few cases. Here, we investigate the role of neuropeptides in the defence behaviour of brachiopod larvae. When mechanically disturbed,the planktonic larvae of Terebratalia transversa protrude their stiff chaetae and sink down slowly. We identified endogenous FLRFamide-type neuropeptides (AFLRFamide and DFLRFamide) in T. transversa larvae and showthat the protrusion of the chaetae as well as the sinking reaction can both be induced by each of these peptides. This also correlates with the presence of FLRFamidergic neurons in the apical lobe and adjacent to the trunk musculature. We deorphanized the AFLRFamide/DFLRFamide receptor and detected its expression in the same tissues. Furthermore, the ability of native and modified FLRFamidetype peptides to activate this receptor was found to correspond with their ability to trigger behavioural responses. Our results show how FLRFamidetype neuropeptides can induce two coherent sub-reactions in a larva with a simple nervous system.
Abstract.
Bauknecht P, Jékely G (2017). Ancient coexistence of norepinephrine, tyramine, and octopamine signaling in bilaterians.
BMC Biology,
15(1).
Abstract:
Ancient coexistence of norepinephrine, tyramine, and octopamine signaling in bilaterians
Background: Norepinephrine/noradrenaline is a neurotransmitter implicated in arousal and other aspects of vertebrate behavior and physiology. In invertebrates, adrenergic signaling is considered absent and analogous functions are performed by the biogenic amines octopamine and its precursor tyramine. These chemically similar transmitters signal by related families of G-protein-coupled receptors in vertebrates and invertebrates, suggesting that octopamine/tyramine are the invertebrate equivalents of vertebrate norepinephrine. However, the evolutionary relationships and origin of these transmitter systems remain unclear. Results: Using phylogenetic analysis and receptor pharmacology, here we have established that norepinephrine, octopamine, and tyramine receptors coexist in some marine invertebrates. In the protostomes Platynereis dumerilii (an annelid) and Priapulus caudatus (a priapulid), we have identified and pharmacologically characterized adrenergic α1 and α2 receptors that coexist with octopamine α, octopamine β, tyramine type 1, and tyramine type 2 receptors. These receptors represent the first examples of adrenergic receptors in protostomes. In the deuterostome Saccoglossus kowalevskii (a hemichordate), we have identified and characterized octopamine α, octopamine β, tyramine type 1, and tyramine type 2 receptors, representing the first examples of these receptors in deuterostomes. S. kowalevskii also has adrenergic α1 and α2 receptors, indicating that all three signaling systems coexist in this animal. In phylogenetic analysis, we have also identified adrenergic and tyramine receptor orthologs in xenacoelomorphs. Conclusions: Our results clarify the history of monoamine signaling in bilaterians. Given that all six receptor families (two each for octopamine, tyramine, and norepinephrine) can be found in representatives of the two major clades of Bilateria, the protostomes and the deuterostomes, all six receptors must have coexisted in the last common ancestor of the protostomes and deuterostomes. Adrenergic receptors were lost from most insects and nematodes, and tyramine and octopamine receptors were lost from most deuterostomes. This complex scenario of differential losses cautions that octopamine signaling in protostomes is not a good model for adrenergic signaling in deuterostomes, and that studies of marine animals where all three transmitter systems coexist will be needed for a better understanding of the origin and ancestral functions of these transmitters.
Abstract.
Bosch TCG, Klimovich A, Domazet-Lošo T, Gründer S, Holstein TW, Jékely G, Miller DJ, Murillo-Rincon AP, Rentzsch F, Richards GS, et al (2017). Back to the Basics: Cnidarians Start to Fire.
Trends in Neurosciences,
40(2), 92-105.
Abstract:
Back to the Basics: Cnidarians Start to Fire
The nervous systems of cnidarians, pre-bilaterian animals that diverged close to the base of the metazoan radiation, are structurally simple and thus have great potential to reveal fundamental principles of neural circuits. Unfortunately, cnidarians have thus far been relatively intractable to electrophysiological and genetic techniques and consequently have been largely passed over by neurobiologists. However, recent advances in molecular and imaging methods are fueling a renaissance of interest in and research into cnidarians nervous systems. Here, we review current knowledge on the nervous systems of cnidarian species and propose that researchers should seize this opportunity and undertake the study of members of this phylum as strategic experimental systems with great basic and translational relevance for neuroscience.
Abstract.
Verasztó C, Ueda N, Bezares-Calderón LA, Panzera A, Williams EA, Shahidi R, Jékely G (2017). Ciliomotor circuitry underlying whole-body coordination of ciliary activity in the platynereis larva.
eLife,
6Abstract:
Ciliomotor circuitry underlying whole-body coordination of ciliary activity in the platynereis larva
Ciliated surfaces harbouring synchronously beating cilia can generate fluid flow or drive locomotion. In ciliary swimmers, ciliary beating, arrests, and changes in beat frequency are often coordinated across extended or discontinuous surfaces. To understand how such coordination is achieved, we studied the ciliated larvae of Platynereis dumerilii, a marine annelid. Platynereis larvae have segmental multiciliated cells that regularly display spontaneous coordinated ciliary arrests. We used whole-body connectomics, activity imaging, transgenesis, and neuron ablation to characterize the ciliomotor circuitry. We identified cholinergic, serotonergic, and catecholaminergic ciliomotor neurons. The synchronous rhythmic activation of cholinergic cells drives the coordinated arrests of all cilia. The serotonergic cells are active when cilia are beating. Serotonin inhibits the cholinergic rhythm, and increases ciliary beat frequency. Based on their connectivity and alternating activity, the catecholaminergic cells may generate the rhythm. The ciliomotor circuitry thus constitutes a stop-and-go pacemaker system for the whole-body coordination of ciliary locomotion.
Abstract.
Kerbl A, Conzelmann M, Jékely G, Worsaae K (2017). High diversity in neuropeptide immunoreactivity patterns among three closely related species of Dinophilidae (Annelida).
J Comp Neurol,
525(17), 3596-3635.
Abstract:
High diversity in neuropeptide immunoreactivity patterns among three closely related species of Dinophilidae (Annelida).
Neuropeptides are conserved metazoan signaling molecules, and represent useful markers for comparative investigations on the morphology and function of the nervous system. However, little is known about the variation of neuropeptide expression patterns across closely related species in invertebrate groups other than insects. In this study, we compare the immunoreactivity patterns of 14 neuropeptides in three closely related microscopic dinophilid annelids (Dinophilus gyrociliatus, D. taeniatus and Trilobodrilus axi). The brains of all three species were found to consist of around 700 somata, surrounding a central neuropil with 3-5 ventral and 2-5 dorsal commissures. Neuropeptide immunoreactivity was detected in the brain, the ventral cords, stomatogastric nervous system, and additional nerves. Different neuropeptides are expressed in specific, non-overlapping cells in the brain in all three species. FMRFamide, MLD/pedal peptide, allatotropin, RNamide, excitatory peptide, and FVRIamide showed a broad localization within the brain, while calcitonin, SIFamide, vasotocin, RGWamide, DLamide, FLamide, FVamide, MIP, and serotonin were present in fewer cells in demarcated regions. The different markers did not reveal ganglionic subdivisions or physical compartmentalization in any of these microscopic brains. The non-overlapping expression of different neuropeptides may indicate that the regionalization in these uniform, small brains is realized by individual cells, rather than cell clusters, representing an alternative to the lobular organization observed in several macroscopic annelids. Furthermore, despite the similar gross brain morphology, we found an unexpectedly high variation in the expression patterns of neuropeptides across species. This suggests that neuropeptide expression evolves faster than morphology, representing a possible mechanism for the evolutionary divergence of behaviors.
Abstract.
Author URL.
Jekely G (2017).
Story of Genetics, Development and Evolution, The: a Historical Dialogue., World Scientific Publishing Europe Limited.
Abstract:
Story of Genetics, Development and Evolution, The: a Historical Dialogue
Abstract.
Williams EA, Verasztó C, Jasek S, Conzelmann M, Shahidi R, Bauknecht P, Mirabeau O, Jékely G (2017). Synaptic and peptidergic connectome of a neurosecretory center in the annelid brain.
eLife,
6Abstract:
Synaptic and peptidergic connectome of a neurosecretory center in the annelid brain
Neurosecretory centers in animal brains use peptidergic signaling to influence physiology and behavior. Understanding neurosecretory center function requires mapping cell types, synapses, and peptidergic networks. Here we use transmission electron microscopy and gene expression mapping to analyze the synaptic and peptidergic connectome of an entire neurosecretory center. We reconstructed 78 neurosecretory neurons and mapped their synaptic connectivity in the brain of larval Platynereis dumerilii, a marine annelid. These neurons form an anterior neurosecretory center expressing many neuropeptides, including hypothalamic peptide orthologs and their receptors. Analysis of peptide-receptor pairs in spatially mapped single-cell transcriptome data revealed sparsely connected networks linking specific neuronal subsets. We experimentally analyzed one peptide-receptor pair and found that a neuropeptide can couple neurosecretory and synaptic brain signaling. Our study uncovered extensive networks of peptidergic signaling within a neurosecretory center and its connection to the synaptic brain.
Abstract.
2016
Thiel D, Jekely G, Hejnol A (2016). Changing the mode: neuropeptide evolution in trochozoans.
Author URL.
Randel N, Jékely G (2016). Phototaxis and the origin of visual eyes.
Philos Trans R Soc Lond B Biol Sci,
371(1685).
Abstract:
Phototaxis and the origin of visual eyes.
Vision allows animals to detect spatial differences in environmental light levels. High-resolution image-forming eyes evolved from low-resolution eyes via increases in photoreceptor cell number, improvements in optics and changes in the neural circuits that process spatially resolved photoreceptor input. However, the evolutionary origins of the first low-resolution visual systems have been unclear. We propose that the lowest resolving (two-pixel) visual systems could initially have functioned in visual phototaxis. During visual phototaxis, such elementary visual systems compare light on either side of the body to regulate phototactic turns. Another, even simpler and non-visual strategy is characteristic of helical phototaxis, mediated by sensory-motor eyespots. The recent mapping of the complete neural circuitry (connectome) of an elementary visual system in the larva of the annelid Platynereis dumerilii sheds new light on the possible paths from non-visual to visual phototaxis and to image-forming vision. We outline an evolutionary scenario focusing on the neuronal circuitry to account for these transitions. We also present a comprehensive review of the structure of phototactic eyes in invertebrate larvae and assign them to the non-visual and visual categories. We propose that non-visual systems may have preceded visual phototactic systems in evolution that in turn may have repeatedly served as intermediates during the evolution of image-forming eyes.
Abstract.
Author URL.
Bezares-Calderón LA, Jékely G (2016). Think small.
Elife,
5Abstract:
Think small.
The tadpole larva of a sea squirt is only the second animal to have its entire nervous system mapped out, and the results confirm that there is still much to learn from the smallest brains.
Abstract.
Author URL.
Williams EA, Jékely G (2016). Towards a systems-level understanding of development in the marine annelid Platynereis dumerilii.
Current Opinion in Genetics and Development,
39, 175-181.
Abstract:
Towards a systems-level understanding of development in the marine annelid Platynereis dumerilii
Platynereis dumerilii is a segmented marine worm from the phylum Annelida, a member of the Lophotrochozoans. Platynereis is easily maintained in the lab and exhibits a highly stereotypic development through spiral cleavage with a small, transparent, free-swimming larva highly suitable for microscopy studies. A protocol for embryo microinjection in Platynereis has enabled several genetic tools to be developed, paving the way for functional studies. Recent Platynereis studies have provided insights into the function of several signaling pathways in development. Platynereis has also proven a useful model system for comparative evolutionary developmental studies, allowing the formation of new hypotheses on the evolution of neuroendocrine signaling, body patterning, and organ development. Combining existing large datasets of spatial gene expression mapping, cell lineage mapping, and neuronal circuits with functional analyses of developmental genes represents a promising approach for future studies aiming at a systems-level understanding of development in Platynereis.
Abstract.
2015
Shahidi R, Williams EA, Conzelmann M, Asadulina A, Verasztó C, Jasek S, Bezares-Calderón LA, Jékely G (2015). A serial multiplex immunogold labeling method for identifying peptidergic neurons in connectomes.
Elife,
4Abstract:
A serial multiplex immunogold labeling method for identifying peptidergic neurons in connectomes.
Electron microscopy-based connectomics aims to comprehensively map synaptic connections in neural tissue. However, current approaches are limited in their capacity to directly assign molecular identities to neurons. Here, we use serial multiplex immunogold labeling (siGOLD) and serial-section transmission electron microscopy (ssTEM) to identify multiple peptidergic neurons in a connectome. The high immunogenicity of neuropeptides and their broad distribution along axons, allowed us to identify distinct neurons by immunolabeling small subsets of sections within larger series. We demonstrate the scalability of siGOLD by using 11 neuropeptide antibodies on a full-body larval ssTEM dataset of the annelid Platynereis. We also reconstruct a peptidergic circuitry comprising the sensory nuchal organs, found by siGOLD to express pigment-dispersing factor, a circadian neuropeptide. Our approach enables the direct overlaying of chemical neuromodulatory maps onto synaptic connectomic maps in the study of nervous systems.
Abstract.
Author URL.
Jékely G, Keijzer F, Godfrey-Smith P (2015). An option space for early neural evolution.
Philos Trans R Soc Lond B Biol Sci,
370(1684).
Abstract:
An option space for early neural evolution.
The origin of nervous systems has traditionally been discussed within two conceptual frameworks. Input-output models stress the sensory-motor aspects of nervous systems, while internal coordination models emphasize the role of nervous systems in coordinating multicellular activity, especially muscle-based motility. Here we consider both frameworks and apply them to describe aspects of each of three main groups of phenomena that nervous systems control: behaviour, physiology and development. We argue that both frameworks and all three aspects of nervous system function need to be considered for a comprehensive discussion of nervous system origins. This broad mapping of the option space enables an overview of the many influences and constraints that may have played a role in the evolution of the first nervous systems.
Abstract.
Author URL.
Doumpas N, Jékely G, Teleman AA (2015). Erratum to: Wnt6 is required for maxillary palp formation in Drosophila.
BMC Biol,
13 Author URL.
Randel N, Shahidi R, Verasztó C, Bezares-Calderón LA, Schmidt S, Jékely G (2015). Inter-individual stereotypy of the Platynereis larval visual connectome.
Elife,
4Abstract:
Inter-individual stereotypy of the Platynereis larval visual connectome.
Developmental programs have the fidelity to form neural circuits with the same structure and function among individuals of the same species. It is less well understood, however, to what extent entire neural circuits of different individuals are similar. Previously, we reported the neuronal connectome of the visual eye circuit from the head of a Platynereis dumerilii larva (Randel et al. 2014). We now report a full-body serial section transmission electron microscopy (ssTEM) dataset of another larva of the same age, for which we describe the connectome of the visual eyes and the larval eyespots. Anatomical comparisons and quantitative analyses of the two circuits reveal a high inter-individual stereotypy of the cell complement, neuronal projections, and synaptic connectivity, including the left-right asymmetry in the connectivity of some neurons. Our work shows the extent to which the eye circuitry in Platynereis larvae is hard-wired.
Abstract.
Author URL.
Bauknecht P, Jékely G (2015). Large-Scale Combinatorial Deorphanization of Platynereis Neuropeptide GPCRs.
Cell Rep,
12(4), 684-693.
Abstract:
Large-Scale Combinatorial Deorphanization of Platynereis Neuropeptide GPCRs.
Neuropeptides, representing the largest class of neuromodulators, commonly signal by G-protein-coupled receptors (GPCRs). While the neuropeptide repertoire of several metazoans has been characterized, many GPCRs are orphans. Here, we develop a strategy to identify GPCR-peptide pairs using combinatorial screening with complex peptide mixtures. We screened 126 neuropeptides against 87 GPCRs of the annelid Platynereis and identified ligands for 19 receptors. We assigned many GPCRs to known families and identified conserved families of achatin, FMRFamide, RGWamide, FLamide, and elevenin receptors. We also identified a ligand for the Platynereis ortholog of vertebrate thyrotropin-releasing hormone (TRH) receptors, revealing the ancient origin of TRH-receptor signaling. We predicted ligands for several metazoan GPCRs and tested predicted achatin receptors. These receptors were specifically activated by an achatin D-peptide, revealing a conserved mode of activation. Our work establishes an important resource and provides information about the complexity of peptidergic signaling in the urbilaterian.
Abstract.
Author URL.
Williams EA, Conzelmann M, Jékely G (2015). Myoinhibitory peptide regulates feeding in the marine annelid Platynereis.
Front Zool,
12(1).
Abstract:
Myoinhibitory peptide regulates feeding in the marine annelid Platynereis.
BACKGROUND: During larval settlement and metamorphosis, marine invertebrates undergo changes in habitat, morphology, behavior and physiology. This change between life-cycle stages is often associated with a change in diet or a transition between a non-feeding and a feeding form. How larvae regulate changes in feeding during this life-cycle transition is not well understood. Neuropeptides are known to regulate several aspects of feeding, such as food search, ingestion and digestion. The marine annelid Platynereis dumerilii has a complex life cycle with a pelagic non-feeding larval stage and a benthic feeding postlarval stage, linked by the process of settlement. The conserved neuropeptide myoinhibitory peptide (MIP) is a key regulator of larval settlement behavior in Platynereis. Whether MIP also regulates the initiation of feeding, another aspect of the pelagic-to-benthic transition in Platynereis, is currently unknown. RESULTS: Here, we explore the contribution of MIP to the regulation of feeding behavior in settled Platynereis postlarvae. We find that in addition to expression in the brain, MIP is expressed in the gut of developing larvae in sensory neurons that densely innervate the hindgut, the foregut, and the midgut. Activating MIP signaling by synthetic neuropeptide addition causes increased gut peristalsis and more frequent pharynx extensions leading to increased food intake. Conversely, morpholino-mediated knockdown of MIP expression inhibits feeding. In the long-term, treatment of Platynereis postlarvae with synthetic MIP increases growth rate and results in earlier cephalic metamorphosis. CONCLUSIONS: Our results show that MIP activates ingestion and gut peristalsis in Platynereis postlarvae. MIP is expressed in enteroendocrine cells of the digestive system suggesting that following larval settlement, feeding may be initiated by a direct sensory-neurosecretory mechanism. This is similar to the mechanism by which MIP induces larval settlement. The pleiotropic roles of MIP may thus have evolved by redeploying the same signaling mechanism in different aspects of a life-cycle transition.
Abstract.
Author URL.
Asadulina A, Conzelmann M, Williams EA, Panzera A, Jékely G (2015). Object-based representation and analysis of light and electron microscopic volume data using Blender.
BMC Bioinformatics,
16Abstract:
Object-based representation and analysis of light and electron microscopic volume data using Blender.
BACKGROUND: Rapid improvements in light and electron microscopy imaging techniques and the development of 3D anatomical atlases necessitate new approaches for the visualization and analysis of image data. Pixel-based representations of raw light microscopy data suffer from limitations in the number of channels that can be visualized simultaneously. Complex electron microscopic reconstructions from large tissue volumes are also challenging to visualize and analyze. RESULTS: Here we exploit the advanced visualization capabilities and flexibility of the open-source platform Blender to visualize and analyze anatomical atlases. We use light-microscopy-based gene expression atlases and electron microscopy connectome volume data from larval stages of the marine annelid Platynereis dumerilii. We build object-based larval gene expression atlases in Blender and develop tools for annotation and coexpression analysis. We also represent and analyze connectome data including neuronal reconstructions and underlying synaptic connectivity. CONCLUSIONS: We demonstrate the power and flexibility of Blender for visualizing and exploring complex anatomical atlases. The resources we have developed for Platynereis will facilitate data sharing and the standardization of anatomical atlases for this species. The flexibility of Blender, particularly its embedded Python application programming interface, means that our methods can be easily extended to other organisms.
Abstract.
Author URL.
Hanswillemenke A, Kuzdere T, Vogel P, Jékely G, Stafforst T (2015). Site-Directed RNA Editing in Vivo can be Triggered by the Light-Driven Assembly of an Artificial Riboprotein.
J Am Chem Soc,
137(50), 15875-15881.
Abstract:
Site-Directed RNA Editing in Vivo can be Triggered by the Light-Driven Assembly of an Artificial Riboprotein.
Site-directed RNA editing allows for the manipulation of RNA and protein function by reprogramming genetic information at the RNA level. For this we assemble artificial RNA-guided editases and demonstrate their transcript repair activity in cells and in developing embryos of the annelid Platynereis dumerilii. A hallmark of our assembly strategy is the covalent attachment of guideRNA and editing enzyme by applying the SNAP-tag technology, a process that we demonstrate here to be readily triggered by light in vitro, in mammalian cell culture, and also in P. dumerilii. Lacking both sophisticated chemistry and extensive genetic engineering, this technology provides a convenient route for the light-dependent switching of protein isoforms. The presented strategy may also serve as a blue-print for the engineering of addressable machineries that apply tailored nucleic acid analogues to manipulate RNA or DNA site-specifically in living organisms.
Abstract.
Author URL.
Gühmann M, Jia H, Randel N, Verasztó C, Bezares-Calderón LA, Michiels NK, Yokoyama S, Jékely G (2015). Spectral Tuning of Phototaxis by a Go-Opsin in the Rhabdomeric Eyes of Platynereis.
Curr Biol,
25(17), 2265-2271.
Abstract:
Spectral Tuning of Phototaxis by a Go-Opsin in the Rhabdomeric Eyes of Platynereis.
Phototaxis is characteristic of the pelagic larval stage of most bottom-dwelling marine invertebrates. Larval phototaxis is mediated by simple eyes that can express various types of light-sensitive G-protein-coupled receptors known as opsins. Since opsins diversified early during metazoan evolution in the marine environment, understanding underwater light detection could elucidate this diversification. Opsins have been classified into three major families, the r-opsins, the c-opsins, and the Go/RGR opsins, a family uniting Go-opsins, retinochromes, RGR opsins, and neuropsins. The Go-opsins form an ancient and poorly characterized group retained only in marine invertebrate genomes. Here, we characterize a Go-opsin from the marine annelid Platynereis dumerilii. We found Go-opsin1 coexpressed with two r-opsins in depolarizing rhabdomeric photoreceptor cells in the pigmented eyes of Platynereis larvae. We purified recombinant Go-opsin1 and found that it absorbs in the blue-cyan range of the light spectrum. To characterize the function of Go-opsin1, we generated a Go-opsin1 knockout Platynereis line by zinc-finger-nuclease-mediated genome engineering. Go-opsin1 knockout larvae were phototactic but showed reduced efficiency of phototaxis to wavelengths matching the in vitro Go-opsin1 spectrum. Our results highlight spectral tuning of phototaxis as a potential mechanism contributing to opsin diversity.
Abstract.
Author URL.
Jékely G, Paps J, Nielsen C (2015). The phylogenetic position of ctenophores and the origin(s) of nervous systems.
Evodevo,
6Abstract:
The phylogenetic position of ctenophores and the origin(s) of nervous systems.
Ctenophores have traditionally been treated as eumetazoans, but some recent whole genome studies have revived the idea that they are, rather, the sister group to all other metazoans. This deep branching position implies either that nervous systems have evolved twice, in Ctenophora and in Eumetazoa, or that an ancestral metazoan nervous system has been lost in sponges and placozoans. We caution, however, that phylogenetic-tree construction artifacts may have placed ctenophores too deep in the metazoan tree. We discuss nervous system origins under these alternative phylogenies and in light of comparative data of ctenophore and eumetazoan nervous systems. We argue that characters like neuropeptide signaling, ciliary photoreceptors, gap junctions and presynaptic molecules are consistent with a shared ancestry of nervous systems. However, if ctenophores are the sister group to all other metazoans, this ancestral nervous system was likely very simple. Further studies are needed to resolve the deep phylogeny of metazoans and to have a better understanding of the early steps of nervous system evolution.
Abstract.
Author URL.
2014
Randel N, Asadulina A, Bezares-Calderón LA, Verasztó C, Williams EA, Conzelmann M, Shahidi R, Jékely G (2014). Neuronal connectome of a sensory-motor circuit for visual navigation.
Elife,
3Abstract:
Neuronal connectome of a sensory-motor circuit for visual navigation.
Animals use spatial differences in environmental light levels for visual navigation; however, how light inputs are translated into coordinated motor outputs remains poorly understood. Here we reconstruct the neuronal connectome of a four-eye visual circuit in the larva of the annelid Platynereis using serial-section transmission electron microscopy. In this 71-neuron circuit, photoreceptors connect via three layers of interneurons to motorneurons, which innervate trunk muscles. By combining eye ablations with behavioral experiments, we show that the circuit compares light on either side of the body and stimulates body bending upon left-right light imbalance during visual phototaxis. We also identified an interneuron motif that enhances sensitivity to different light intensity contrasts. The Platynereis eye circuit has the hallmarks of a visual system, including spatial light detection and contrast modulation, illustrating how image-forming eyes may have evolved via intermediate stages contrasting only a light and a dark field during a simple visual task.
Abstract.
Author URL.
Jékely G (2014). Origin and evolution of the self-organizing cytoskeleton in the network of eukaryotic organelles.
Cold Spring Harb Perspect Biol,
6(9).
Abstract:
Origin and evolution of the self-organizing cytoskeleton in the network of eukaryotic organelles.
The eukaryotic cytoskeleton evolved from prokaryotic cytomotive filaments. Prokaryotic filament systems show bewildering structural and dynamic complexity and, in many aspects, prefigure the self-organizing properties of the eukaryotic cytoskeleton. Here, the dynamic properties of the prokaryotic and eukaryotic cytoskeleton are compared, and how these relate to function and evolution of organellar networks is discussed. The evolution of new aspects of filament dynamics in eukaryotes, including severing and branching, and the advent of molecular motors converted the eukaryotic cytoskeleton into a self-organizing "active gel," the dynamics of which can only be described with computational models. Advances in modeling and comparative genomics hold promise of a better understanding of the evolution of the self-organizing cytoskeleton in early eukaryotes, and its role in the evolution of novel eukaryotic functions, such as amoeboid motility, mitosis, and ciliary swimming.
Abstract.
Author URL.
2013
Conzelmann M, Williams EA, Tunaru S, Randel N, Shahidi R, Asadulina A, Berger J, Offermanns S, Jékely G (2013). Conserved MIP receptor-ligand pair regulates Platynereis larval settlement.
Proc Natl Acad Sci U S A,
110(20), 8224-8229.
Abstract:
Conserved MIP receptor-ligand pair regulates Platynereis larval settlement.
Life-cycle transitions connecting larval and juvenile stages in metazoans are orchestrated by neuroendocrine signals including neuropeptides and hormones. In marine invertebrate life cycles, which often consist of planktonic larval and benthic adult stages, settlement of the free-swimming larva to the sea floor in response to environmental cues is a key life cycle transition. Settlement is regulated by a specialized sensory-neurosecretory system, the larval apical organ. The neuroendocrine mechanisms through which the apical organ transduces environmental cues into behavioral responses during settlement are not yet understood. Here we show that myoinhibitory peptide (MIP)/allatostatin-B, a pleiotropic neuropeptide widespread among protostomes, regulates larval settlement in the marine annelid Platynereis dumerilii. MIP is expressed in chemosensory-neurosecretory cells in the annelid larval apical organ and signals to its receptor, an orthologue of the Drosophila sex peptide receptor, expressed in neighboring apical organ cells. We demonstrate by morpholino-mediated knockdown that MIP signals via this receptor to trigger settlement. These results reveal a role for a conserved MIP receptor-ligand pair in regulating marine annelid settlement.
Abstract.
Author URL.
Holder T, Basquin C, Ebert J, Randel N, Jollivet D, Conti E, Jékely G, Bono F (2013). Deep transcriptome-sequencing and proteome analysis of the hydrothermal vent annelid Alvinella pompejana identifies the CvP-bias as a robust measure of eukaryotic thermostability.
Biol Direct,
8Abstract:
Deep transcriptome-sequencing and proteome analysis of the hydrothermal vent annelid Alvinella pompejana identifies the CvP-bias as a robust measure of eukaryotic thermostability.
BACKGROUND: Alvinella pompejana is an annelid worm that inhabits deep-sea hydrothermal vent sites in the Pacific Ocean. Living at a depth of approximately 2500 meters, these worms experience extreme environmental conditions, including high temperature and pressure as well as high levels of sulfide and heavy metals. A. pompejana is one of the most thermotolerant metazoans, making this animal a subject of great interest for studies of eukaryotic thermoadaptation. RESULTS: in order to complement existing EST resources we performed deep sequencing of the A. pompejana transcriptome. We identified several thousand novel protein-coding transcripts, nearly doubling the sequence data for this annelid. We then performed an extensive survey of previously established prokaryotic thermoadaptation measures to search for global signals of thermoadaptation in A. pompejana in comparison with mesophilic eukaryotes. In an orthologous set of 457 proteins, we found that the best indicator of thermoadaptation was the difference in frequency of charged versus polar residues (CvP-bias), which was highest in A. pompejana. CvP-bias robustly distinguished prokaryotic thermophiles from prokaryotic mesophiles, as well as the thermophilic fungus Chaetomium thermophilum from mesophilic eukaryotes. Experimental values for thermophilic proteins supported higher CvP-bias as a measure of thermal stability when compared to their mesophilic orthologs. Proteome-wide mean CvP-bias also correlated with the body temperatures of homeothermic birds and mammals. CONCLUSIONS: Our work extends the transcriptome resources for A. pompejana and identifies the CvP-bias as a robust and widely applicable measure of eukaryotic thermoadaptation.
Abstract.
Author URL.
Randel N, Bezares-Calderón LA, Gühmann M, Shahidi R, Jékely G (2013). Expression dynamics and protein localization of rhabdomeric opsins in Platynereis larvae.
Integr Comp Biol,
53(1), 7-16.
Abstract:
Expression dynamics and protein localization of rhabdomeric opsins in Platynereis larvae.
The larval stages of polychaete annelids are often responsive to light and can possess one to six eyes. The early trochophore larvae of the errant annelid Platynereis dumerilii have a single pair of ventral eyespots, whereas older nectochaete larvae have an additional two pairs of dorsal eyes that will develop into the adult eyes. Early Platynereis trochophores show robust positive phototaxis starting on the first day of development. Even though the mechanism of phototaxis in Platynereis early trochophore larvae is well understood, no photopigment (opsin) expression has yet been described in this stage. In late trochophore larvae, a rhabdomeric-type opsin, r-opsin1, expressed in both the eyespots and the adult eyes has already been reported. Here, we identify another Platynereis rhabdomeric opsin, r-opsin3, that is expressed in a single photoreceptor in the eyespots in early trochophores, suggesting that it mediates early larval phototaxis. We also show that r-opsin1 and r-opsin3 are expressed in adjacent photoreceptor cells in the eyespots in later stages, indicating that a second eyespot-photoreceptor differentiates in late trochophore larvae. Using serial transmission electron microscopy (TEM), we identified and reconstructed both photoreceptors and a pigment cell in the late larval eyespot. We also characterized opsin expression in the adult eyes and found that the two opsins co-express there in several photoreceptor cells. Using antibodies recognizing r-opsin1 and r-opsin3 proteins, we demonstrate that both opsins localize to the rhabdomere in all six eyes. In addition, we found that r-opsin1 mRNA is localized to, and translated in, the projections of the adult eyes. The specific changes we describe in opsin transcription and translation and in the cellular complement suggest that the six larval eyes undergo spectral and functional maturation during the early planktonic phase of the Platynereis life cycle.
Abstract.
Author URL.
Jékely G (2013). Global view of the evolution and diversity of metazoan neuropeptide signaling.
Proc Natl Acad Sci U S A,
110(21), 8702-8707.
Abstract:
Global view of the evolution and diversity of metazoan neuropeptide signaling.
Neuropeptides are signaling molecules that commonly act via G protein-coupled receptors (GPCRs) and are generated in neurons by proneuropeptide (pNP) cleavage. Present in both cnidarians and bilaterians, neuropeptides represent an ancient and widespread mode of neuronal communication. Due to the inherent difficulties of analyzing highly diverse and repetitive pNPs, the relationships among different families are often elusive. Using similarity-based clustering and sensitive similarity searches, I obtained a global view of metazoan pNP diversity and evolution. Clustering revealed a large and diffuse network of sequences connected by significant sequence similarity encompassing one-quarter of all families. pNPs belonging to this cluster were also identified in the early-branching neuronless animal Trichoplax adhaerens. Clustering of neuropeptide GPCRs identified several orthology groups and allowed the reconstruction of the phyletic distribution of receptor families. GPCR phyletic distribution closely paralleled that of pNPs, indicating extensive conservation and long-term coevolution of receptor-ligand pairs. Receptor orthology and intermediate sequences also revealed the homology of pNPs so far considered unrelated, including allatotropin and orexin. These findings, together with the identification of deuterostome achatin and luqin and protostome opioid pNPs, extended the neuropeptide complement of the urbilaterian. Several pNPs were also identified from the hemichordate Saccoglossus kowalevskii and the cephalochordate Branchiostoma floridae, elucidating pNP evolution in deuterostomes. Receptor-ligand conservation also allowed ligand predictions for many uncharacterized GPCRs from nonmodel species. The reconstruction of the neuropeptide-signaling repertoire at deep nodes of the animal phylogeny allowed the formulation of a testable scenario of the evolution of animal neuroendocrine systems.
Abstract.
Author URL.
Randel N, JeKely G (2013). Mechanism of negative phototaxis in Platynereis larvae.
Author URL.
Jekely G (2013). Mechanism of phototaxis in marine zooplankton and origin of simple visual circuits.
Author URL.
Lapraz F, Rawlinson KA, Girstmair J, Tomiczek B, Berger J, Jékely G, Telford MJ, Egger B (2013). Put a tiger in your tank: the polyclad flatworm Maritigrella crozieri as a proposed model for evo-devo.
Evodevo,
4(1).
Abstract:
Put a tiger in your tank: the polyclad flatworm Maritigrella crozieri as a proposed model for evo-devo.
Polyclad flatworms are an early branching clade within the rhabditophoran Platyhelminthes. They provide an interesting system with which to explore the evolution of development within Platyhelminthes and amongst Spiralia (Lophotrochozoa). Unlike most other flatworms, polyclads undergo spiral cleavage (similar to that seen in some other spiralian taxa), they are the only free-living flatworms where development via a larval stage occurs, and they are the only flatworms in which embryos can be reared outside of their protective egg case, enabling embryonic manipulations. Past work has focused on comparing early cleavage patterns and larval anatomy between polyclads and other spiralians. We have selected Maritigrella crozieri, the tiger flatworm, as a suitable polyclad species for developmental studies, because it is abundant and large in size compared to other species. These characteristics have facilitated the generation of a transcriptome from embryonic and larval material and are enabling us to develop methods for gene expression analysis and immunofluorescence techniques. Here we give an overview of M. crozieri and its development, we highlight the advantages and current limitations of this animal as a potential evo-devo model and discuss current lines of research.
Abstract.
Author URL.
Conzelmann M, Williams EA, Krug K, Franz-Wachtel M, Macek B, Jékely G (2013). The neuropeptide complement of the marine annelid Platynereis dumerilii.
BMC Genomics,
14Abstract:
The neuropeptide complement of the marine annelid Platynereis dumerilii.
BACKGROUND: the marine annelid Platynereis dumerilii is emerging as a powerful lophotrochozoan experimental model for evolutionary developmental biology (evo-devo) and neurobiology. Recent studies revealed the presence of conserved neuropeptidergic signaling in Platynereis, including vasotocin/neurophysin, myoinhibitory peptide and opioid peptidergic systems. Despite these advances, comprehensive peptidome resources have yet to be reported. RESULTS: the present work describes the neuropeptidome of Platynereis. We established a large transcriptome resource, consisting of stage-specific next-generation sequencing datasets and 77,419 expressed sequence tags. Using this information and a combination of bioinformatic searches and mass spectrometry analyses, we increased the known proneuropeptide (pNP) complement of Platynereis to 98. Based on sequence homology to metazoan pNPs, Platynereis pNPs were grouped into ancient eumetazoan, bilaterian, protostome, lophotrochozoan, and annelid families, and pNPs only found in Platynereis. Compared to the planarian Schmidtea mediterranea, the only other lophotrochozoan with a large-scale pNP resource, Platynereis has a remarkably full complement of conserved pNPs, with 53 pNPs belonging to ancient eumetazoan or bilaterian families. Our comprehensive search strategy, combined with analyses of sequence conservation, also allowed us to define several novel lophotrochozoan and annelid pNP families. The stage-specific transcriptome datasets also allowed us to map changes in pNP expression throughout the Platynereis life cycle. CONCLUSION: the large repertoire of conserved pNPs in Platynereis highlights the usefulness of annelids in comparative neuroendocrinology. This work establishes a reference dataset for comparative peptidomics in lophotrochozoans and provides the basis for future studies of Platynereis peptidergic signaling.
Abstract.
Author URL.
Doumpas N, Jékely G, Teleman AA (2013). Wnt6 is required for maxillary palp formation in Drosophila.
BMC Biol,
11Abstract:
Wnt6 is required for maxillary palp formation in Drosophila.
BACKGROUND: Wnt6 is an evolutionarily ancient member of the Wnt family. In Drosophila, Wnt6 loss-of-function animals have not yet been reported, hence information about fly Wnt6 function is lacking. In wing discs, Wnt6 is expressed at the dorsal/ventral boundary in a pattern similar to that of wingless, an important regulator of wing size. To test whether Wnt6 also contributes towards wing size regulation, we generated Wnt6 knockout flies. RESULTS: Wnt6 knockout flies are viable and have no obvious defect in wing size or planar cell polarity. Surprisingly, Wnt6 knockouts lack maxillary palps. Interestingly, Wnt6 is absent from the genome of hemipterans, correlating with the absence of maxillary palps in these insects. CONCLUSIONS: Wnt6 is important for maxillary palp development in Drosophila, and phylogenetic analysis indicates that loss of Wnt6 may also have led to loss of maxillary palps on an evolutionary time scale.
Abstract.
Author URL.
2012
Conzelmann M, Jékely G (2012). Antibodies against conserved amidated neuropeptide epitopes enrich the comparative neurobiology toolbox.
Evodevo,
3(1).
Abstract:
Antibodies against conserved amidated neuropeptide epitopes enrich the comparative neurobiology toolbox.
BACKGROUND: Neuronal antibodies that show immunoreactivity across a broad range of species are important tools for comparative neuroanatomy. Nonetheless, the current antibody repertoire for non-model invertebrates is limited. Currently, only antibodies against the neuropeptide RFamide and the monoamine transmitter serotonin are extensively used. These antibodies label respective neuron-populations and their axons and dendrites in a large number of species across various animal phyla. RESULTS: Several other neuropeptides also have a broad phyletic distribution among invertebrates, including DLamides, FVamides, FLamides, GWamides and RYamides. These neuropeptides show strong conservation of the two carboxy-terminal amino acids and are α-amidated at their C-termini. We generated and affinity-purified specific polyclonal antibodies against each of these conserved amidated dipeptide motifs. We thoroughly tested antibody reactivity and specificity both by peptide pre-incubation experiments and by showing a close correlation between the immunostaining signals and mRNA expression patterns of the respective precursor genes in the annelid Platynereis. We also demonstrated the usefulness of these antibodies by performing immunostainings on a broad range of invertebrate species, including cnidarians, annelids, molluscs, a bryozoan, and a crustacean. In all species, the antibodies label distinct neuronal populations and their axonal projections. In the ciliated larvae of cnidarians, annelids, molluscs and bryozoans, a subset of antibodies reveal peptidergic innervation of locomotor cilia. CONCLUSIONS: We developed five specific cross-species-reactive antibodies recognizing conserved two-amino-acid amidated neuropeptide epitopes. These antibodies allow specific labelling of peptidergic neurons and their projections in a broad range of invertebrates. Our comparative survey across several marine phyla demonstrates a broad occurrence of peptidergic innervation of larval ciliary bands, suggesting a general role of these neuropeptides in the regulation of ciliary swimming.
Abstract.
Author URL.
Asadulina A, Panzera A, Verasztó C, Liebig C, Jékely G (2012). Whole-body gene expression pattern registration in Platynereis larvae.
Evodevo,
3(1).
Abstract:
Whole-body gene expression pattern registration in Platynereis larvae.
BACKGROUND: Digital anatomical atlases are increasingly used in order to depict different gene expression patterns and neuronal morphologies within a standardized reference template. In evo-devo, a discipline in which the comparison of gene expression patterns is a widely used approach, such standardized anatomical atlases would allow a more rigorous assessment of the conservation of and changes in gene expression patterns during micro- and macroevolutionary time scales. Due to its small size and invariant early development, the annelid Platynereis dumerilii is particularly well suited for such studies. Recently a reference template with registered gene expression patterns has been generated for the anterior part (episphere) of the Platynereis trochophore larva and used for the detailed study of neuronal development. RESULTS: Here we introduce and evaluate a method for whole-body gene expression pattern registration for Platynereis trochophore and nectochaete larvae based on whole-mount in situ hybridization, confocal microscopy, and image registration. We achieved high-resolution whole-body scanning using the mounting medium 2,2'-thiodiethanol (TDE), which allows the matching of the refractive index of the sample to that of glass and immersion oil thereby reducing spherical aberration and improving depth penetration. This approach allowed us to scan entire whole-mount larvae stained with nitroblue tetrazolium/5-bromo-4-chloro-3-indolyl phosphate (NBT/BCIP) in situ hybridization and counterstained fluorescently with an acetylated-tubulin antibody and the nuclear stain 4'6-diamidino-2-phenylindole (DAPI). Due to the submicron isotropic voxel size whole-mount larvae could be scanned in any orientation. Based on the whole-body scans, we generated four different reference templates by the iterative registration and averaging of 40 individual image stacks using either the acetylated-tubulin or the nuclear-stain signal for each developmental stage. We then registered to these templates the expression patterns of cell-type specific genes. In order to evaluate the gene expression pattern registration, we analyzed the absolute deviation of cell-center positions. Both the acetylated-tubulin- and the nuclear-stain-based templates allowed near-cellular-resolution gene expression registration. Nuclear-stain-based templates often performed significantly better than acetylated-tubulin-based templates. We provide detailed guidelines and scripts for the use and further expansion of the Platynereis gene expression atlas. CONCLUSIONS: We established whole-body reference templates for the generation of gene expression atlases for Platynereis trochophore and nectochaete larvae. We anticipate that nuclear-staining-based image registration will be applicable for whole-body alignment of the embryonic and larval stages of other organisms in a similar size range.
Abstract.
Author URL.
2011
Conzelmann M, Offenburger S-L, Asadulina A, Keller T, Münch TA, Jékely G (2011). Neuropeptides regulate swimming depth of Platynereis larvae.
Proc Natl Acad Sci U S A,
108(46), E1174-E1183.
Abstract:
Neuropeptides regulate swimming depth of Platynereis larvae.
Cilia-based locomotion is the major form of locomotion for microscopic planktonic organisms in the ocean. Given their negative buoyancy, these organisms must control ciliary activity to maintain an appropriate depth. The neuronal bases of depth regulation in ciliary swimmers are unknown. To gain insights into depth regulation we studied ciliary locomotor control in the planktonic larva of the marine annelid, Platynereis. We found several neuropeptides expressed in distinct sensory neurons that innervate locomotor cilia. Neuropeptides altered ciliary beat frequency and the rate of calcium-evoked ciliary arrests. These changes influenced larval orientation, vertical swimming, and sinking, resulting in upward or downward shifts in the steady-state vertical distribution of larvae. Our findings indicate that Platynereis larvae have depth-regulating peptidergic neurons that directly translate sensory inputs into locomotor output on effector cilia. We propose that the simple circuitry found in these ciliated larvae represents an ancestral state in nervous system evolution.
Abstract.
Author URL.
Jékely G (2011). Origin and early evolution of neural circuits for the control of ciliary locomotion.
Proc Biol Sci,
278(1707), 914-922.
Abstract:
Origin and early evolution of neural circuits for the control of ciliary locomotion.
Behaviour evolved before nervous systems. Various single-celled eukaryotes (protists) and the ciliated larvae of sponges devoid of neurons can display sophisticated behaviours, including phototaxis, gravitaxis or chemotaxis. In single-celled eukaryotes, sensory inputs directly influence the motor behaviour of the cell. In swimming sponge larvae, sensory cells influence the activity of cilia on the same cell, thereby steering the multicellular larva. In these organisms, the efficiency of sensory-to-motor transformation (defined as the ratio of sensory cells to total cell number) is low. With the advent of neurons, signal amplification and fast, long-range communication between sensory and motor cells became possible. This may have first occurred in a ciliated swimming stage of the first eumetazoans. The first axons may have had en passant synaptic contacts to several ciliated cells to improve the efficiency of sensory-to-motor transformation, thereby allowing a reduction in the number of sensory cells tuned for the same input. This could have allowed the diversification of sensory modalities and of the behavioural repertoire. I propose that the first nervous systems consisted of combined sensory-motor neurons, directly translating sensory input into motor output on locomotor ciliated cells and steering muscle cells. Neuronal circuitry with low levels of integration has been retained in cnidarians and in the ciliated larvae of some marine invertebrates. This parallel processing stage could have been the starting point for the evolution of more integrated circuits performing the first complex computations such as persistence or coincidence detection. The sensory-motor nervous systems of cnidarians and ciliated larvae of diverse phyla show that brains, like all biological structures, are not irreducibly complex.
Abstract.
Author URL.
2009
Jékely G (2009). Evolution of phototaxis.
Philos Trans R Soc Lond B Biol Sci,
364(1531), 2795-2808.
Abstract:
Evolution of phototaxis.
Phototaxis in the broadest sense means positive or negative displacement along a light gradient or vector. Prokaryotes most often use a biased random walk strategy, employing type I sensory rhodopsin photoreceptors and two-component signalling to regulate flagellar reversal. This strategy only allows phototaxis along steep light gradients, as found in microbial mats or sediments. Some filamentous cyanobacteria evolved the ability to steer towards a light vector. Even these cyanobacteria, however, can only navigate in two dimensions, gliding on a surface. In contrast, eukaryotes evolved the capacity to follow a light vector in three dimensions in open water. This strategy requires a polarized organism with a stable form, helical swimming with cilia and a shading or focusing body adjacent to a light sensor to allow for discrimination of light direction. Such arrangement and the ability of three-dimensional phototactic navigation evolved at least eight times independently in eukaryotes. The origin of three-dimensional phototaxis often followed a transition from a benthic to a pelagic lifestyle and the acquisition of chloroplasts either via primary or secondary endosymbiosis. Based on our understanding of the mechanism of phototaxis in single-celled eukaryotes and animal larvae, it is possible to define a series of elementary evolutionary steps, each of potential selective advantage, which can lead to pelagic phototactic navigation. We can conclude that it is relatively easy to evolve phototaxis once cell polarity, ciliary swimming and a stable cell shape are present.
Abstract.
Author URL.
Arendt D, Denes AS, Jékely G, Tessmar-Raible K (2009). The evolution of nervous system centralization. In (Ed)
Animal Evolution: Genomes, Fossils, and Trees.
Abstract:
The evolution of nervous system centralization
Abstract.
2008
Arendt D, Tomer R, Denes A, Jekely G, Raible F (2008). Annelid Neurodevelopment Supports Dohrn's "Annelid Theory" for the Origin of Vertebrates.
Author URL.
Jékely G (2008). Evolution of the Golgi complex. In (Ed)
The Golgi Apparatus: State of the Art 110 Years after Camillo Golgi's Discovery, 675-691.
Abstract:
Evolution of the Golgi complex
Abstract.
Satir P, Mitchell DR, Jékely G (2008). How did the cilium evolve?.
Curr Top Dev Biol,
85, 63-82.
Abstract:
How did the cilium evolve?
The cilium is a characteristic organelle of eukaryotes constructed from over 600 proteins. Bacterial flagella are entirely different. 9 + 2 motile cilia evolved before the divergence of the last eukaryotic common ancestor (LECA). This chapter explores, compares, and contrasts two potential pathways of evolution: (1) via invasion of a centriolar-like virus and (2) via autogenous formation from a pre-existing microtubule-organizing center (MTOC). In either case, the intraflagellar transport (IFT) machinery that is nearly universally required for the assembly and maintenance of cilia derived from the evolving intracellular vesicular transport system. The sensory function of cilia evolved first and the ciliary axoneme evolved gradually with ciliary motility, an important selection mechanism, as one of the driving forces.
Abstract.
Author URL.
Jékely G, Colombelli J, Hausen H, Guy K, Stelzer E, Nédélec F, Arendt D (2008). Mechanism of phototaxis in marine zooplankton.
Nature,
456(7220), 395-399.
Abstract:
Mechanism of phototaxis in marine zooplankton.
The simplest animal eyes are eyespots composed of two cells only: a photoreceptor and a shading pigment cell. They resemble Darwin's 'proto-eyes', considered to be the first eyes to appear in animal evolution. Eyespots cannot form images but enable the animal to sense the direction of light. They are characteristic for the zooplankton larvae of marine invertebrates and are thought to mediate larval swimming towards the light. Phototaxis of invertebrate larvae contributes to the vertical migration of marine plankton, which is thought to represent the biggest biomass transport on Earth. Yet, despite its ecological and evolutionary importance, the mechanism by which eyespots regulate phototaxis is poorly understood. Here we show how simple eyespots in marine zooplankton mediate phototactic swimming, using the marine annelid Platynereis dumerilii as a model. We find that the selective illumination of one eyespot changes the beating of adjacent cilia by direct cholinergic innervation resulting in locally reduced water flow. Computer simulations of larval swimming show that these local effects are sufficient to direct the helical swimming trajectories towards the light. The computer model also shows that axial rotation of the larval body is essential for phototaxis and that helical swimming increases the precision of navigation. These results provide, to our knowledge, the first mechanistic understanding of phototaxis in a marine zooplankton larva and show how simple eyespots regulate it. We propose that the underlying direct coupling of light sensing and ciliary locomotor control was a principal feature of the proto-eye and an important landmark in the evolution of animal eyes.
Abstract.
Author URL.
Jékely G (2008). Origin of the nucleus and Ran-dependent transport to safeguard ribosome biogenesis in a chimeric cell.
Biol Direct,
3Abstract:
Origin of the nucleus and Ran-dependent transport to safeguard ribosome biogenesis in a chimeric cell.
BACKGROUND: the origin of the nucleus is a central problem about the origin of eukaryotes. The common ancestry of nuclear pore complexes (NPC) and vesicle coating complexes indicates that the nucleus evolved via the modification of a pre-existing endomembrane system. Such an autogenous scenario is cell biologically feasible, but it is not clear what were the selective or neutral mechanisms that had led to the origin of the nuclear compartment. RESULTS: a key selective force during the autogenous origin of the nucleus could have been the need to segregate ribosome factories from the cytoplasm where ribosomal proteins (RPs) of the protomitochondrium were synthesized. After its uptake by an anuclear cell the protomitochondrium transferred several of its RP genes to the host genome. Alphaproteobacterial RPs and archaebacterial-type host ribosomes were consequently synthesized in the same cytoplasm. This could have led to the formation of chimeric ribosomes. I propose that the nucleus evolved when the host cell compartmentalised its ribosome factories and the tightly linked genome to reduce ribosome chimerism. This was achieved in successive stages by first evolving karyopherin and RanGTP dependent chaperoning of RPs, followed by the evolution of a membrane network to serve as a diffusion barrier, and finally a hydrogel sieve to ensure selective permeability at nuclear pores. Computer simulations show that a gradual segregation of cytoplasm and nucleoplasm via these steps can progressively reduce ribosome chimerism. CONCLUSION: Ribosome chimerism can provide a direct link between the selective forces for and the mechanisms of evolving nuclear transport and compartmentalisation. The detailed molecular scenario presented here provides a solution to the gradual evolution of nuclear compartmentalization from an anuclear stage. REVIEWERS: This article was reviewed by Eugene V Koonin, Martijn Huynen, Anthony M. Poole and Patrick Forterre.
Abstract.
Author URL.
Arendt D, Denes AS, Jékely G, Tessmar-Raible K (2008). The evolution of nervous system centralization.
Philos Trans R Soc Lond B Biol Sci,
363(1496), 1523-1528.
Abstract:
The evolution of nervous system centralization.
It is yet unknown when and in what form the central nervous system in Bilateria first came into place and how it further evolved in the different bilaterian phyla. To find out, a series of recent molecular studies have compared neurodevelopment in slow-evolving deuterostome and protostome invertebrates, such as the enteropneust hemichordate Saccoglossus and the polychaete annelid Platynereis. These studies focus on the spatially different activation and, when accessible, function of genes that set up the molecular anatomy of the neuroectoderm and specify neuron types that emerge from distinct molecular coordinates. Complex similarities are detected, which reveal aspects of neurodevelopment that most likely occurred already in a similar manner in the last common ancestor of the bilaterians, Urbilateria. This way, different aspects of the molecular architecture of the urbilaterian nervous system are reconstructed and yield insight into the degree of centralization that was in place in the bilaterian ancestors.
Abstract.
Author URL.
2007
Jékely G, Arendt D (2007). Cellular resolution expression profiling using confocal detection of NBT/BCIP precipitate by reflection microscopy.
Biotechniques,
42(6), 751-755.
Abstract:
Cellular resolution expression profiling using confocal detection of NBT/BCIP precipitate by reflection microscopy.
The determination of gene expression patterns in three dimensions with cellular resolution is an important goal in developmental biology. However the most sensitive, efficient, and widely used staining technique for whole-mount in situ hybridization (WMISH), nitroblue tetrazolium (NBT)/5-bromo-4-chloro-3-indolyl phosphate (BCIP) precipitation by alkaline phosphatase, could not yet be combined with the most precise, high-resolution detection technique, confocal laser-scanning microscopy (CLSM). Here we report the efficient visualization of the NBT/BCIP precipitate using confocal reflection microscopy for WMISH samples of Drosophila, zebrafish, and the marine annelid worm, Platynereis dumerilii. In our simple WMISH protocol for reflection CLSM, NBT/BCIP staining can be combined with fluorescent WMISH, immunostainings, or transgenic green fluorescent protein (GFP) marker lines, allowing double labeling of cell types or of embryological structures of interest. Whole-mount reflection CLSM will thus greatly facilitate large-scale cellular resolution expression profiling in vertebrate and invertebrate model organisms.
Abstract.
Author URL.
Jékely G (2007). Eukaryotic Membranes and Cytoskeleton: Origins and Evolution - Preface.
Denes AS, Jékely G, Steinmetz PRH, Raible F, Snyman H, Prud'homme B, Ferrier DEK, Balavoine G, Arendt D (2007). Molecular architecture of annelid nerve cord supports common origin of nervous system centralization in bilateria.
Cell,
129(2), 277-288.
Abstract:
Molecular architecture of annelid nerve cord supports common origin of nervous system centralization in bilateria.
To elucidate the evolutionary origin of nervous system centralization, we investigated the molecular architecture of the trunk nervous system in the annelid Platynereis dumerilii. Annelids belong to Bilateria, an evolutionary lineage of bilateral animals that also includes vertebrates and insects. Comparing nervous system development in annelids to that of other bilaterians could provide valuable information about the common ancestor of all Bilateria. We find that the Platynereis neuroectoderm is subdivided into longitudinal progenitor domains by partially overlapping expression regions of nk and pax genes. These domains match corresponding domains in the vertebrate neural tube and give rise to conserved neural cell types. As in vertebrates, neural patterning genes are sensitive to Bmp signaling. Our data indicate that this mediolateral architecture was present in the last common bilaterian ancestor and thus support a common origin of nervous system centralization in Bilateria.
Abstract.
Author URL.
Jékely G (2007). Origin of eukaryotic endomembranes: a critical evaluation of different model scenarios.
Adv Exp Med Biol,
607, 38-51.
Abstract:
Origin of eukaryotic endomembranes: a critical evaluation of different model scenarios.
All cells can be assigned to one of two categories based on the complexity of cellular organization, eukaryotes and prokaryotes. Eukaryotes possess, among other distinguishing features, an intracellular dynamic membrane system through which there is a constant flow of membranes scaffolded by an internal cytoskeleton. Prokaryotes, however, can have internal membranes, entirely lack a system that resembles eukaryotic endomembranes in terms of dynamics, complexity and the multitude of functions. How and why did the complex endomembrane system of eukaryotes arise? Here I give a critical overview of the different cell biological model scenarios that have been proposed to explain endomembrane origins. I argue that the widely held symbiotic models for the origin of the nuclear envelope and other endomembranes are cell biologically and evolutionarily highly implausible. Recent findings about the origin of nuclear pore complexes also severely challenge such models. I also criticize a scenario of de novo vesicle formation at the origin of the endomembrane system. I contrast these scenarios to traditional and revised autogenous models according to which eukaryotic endomembranes evolved by the inward budding of a prokaryotic cell's plasma membrane. I argue that such models can best satisfy the major constraints of membrane topology, membrane heredity and straightforwardly account for selection pressures while being consistent with genomic findings.
Abstract.
Author URL.
Jékely G (2007). Origin of phagotrophic eukaryotes as social cheaters in microbial biofilms.
Biol Direct,
2Abstract:
Origin of phagotrophic eukaryotes as social cheaters in microbial biofilms.
BACKGROUND: the origin of eukaryotic cells was one of the most dramatic evolutionary transitions in the history of life. It is generally assumed that eukaryotes evolved later then prokaryotes by the transformation or fusion of prokaryotic lineages. However, as yet there is no consensus regarding the nature of the prokaryotic group(s) ancestral to eukaryotes. Regardless of this, a hardly debatable fundamental novel characteristic of the last eukaryotic common ancestor was the ability to exploit prokaryotic biomass by the ingestion of entire cells, i.e. phagocytosis. The recent advances in our understanding of the social life of prokaryotes may help to explain the origin of this form of total exploitation. PRESENTATION OF THE HYPOTHESIS: Here I propose that eukaryotic cells originated in a social environment, a differentiated microbial mat or biofilm that was maintained by the cooperative action of its members. Cooperation was costly (e.g. the production of developmental signals or an extracellular matrix) but yielded benefits that increased the overall fitness of the social group. I propose that eukaryotes originated as selfish cheaters that enjoyed the benefits of social aggregation but did not contribute to it themselves. The cheaters later evolved into predators that lysed other cells and eventually became professional phagotrophs. During several cycles of social aggregation and dispersal the number of cheaters was contained by a chicken game situation, i.e. reproductive success of cheaters was high when they were in low abundance but was reduced when they were over-represented. Radical changes in cell structure, including the loss of the rigid prokaryotic cell wall and the development of endomembranes, allowed the protoeukaryotes to avoid cheater control and to exploit nutrients more efficiently. Cellular changes were buffered by both the social benefits and the protective physico-chemical milieu of the interior of biofilms. Symbiosis with the mitochondial ancestor evolved after phagotrophy as alphaproteobacterial prey developed post-ingestion defence mechanisms to circumvent digestion in the food vacuole. Mitochondrial symbiosis triggered the origin of the nucleus. Cilia evolved last and allowed eukaryotes to predate also on planktonic prey. I will discuss how this scenario may possibly fit into the contrasting phylogenetic frameworks that have been proposed. TESTING THE HYPOTHESIS: Some aspects of the hypothesis can be tested experimentally by studying the level of exploitation cheaters can reach in social microbes. It would be interesting to test whether absorption of nutrients from lysed fellow colony members can happen and if cheaters can evolve into predators that actively digest neighbouring cells. IMPLICATIONS OF THE HYPOTHESIS: the hypothesis highlights the importance of social exploitation in cell evolution and how a social environment can buffer drastic cellular transformations that would be lethal for planktonic forms.
Abstract.
Author URL.
2006
Jékely G (2006). Did the last common ancestor have a biological membrane?.
Biol Direct,
1Abstract:
Did the last common ancestor have a biological membrane?
All theories about the origin and evolution of membrane bound cells necessarily have to cope with the nature of the last common ancestor of cellular life. One of the most important aspect of this ancestor, whether it had a closed biological membrane or not, has recently been intensely debated. Having a consensus about it would be an important step towards an eventual (though probably still remote) synthesis of the best elements of the current multitude of cell evolution models. Here I analyse the structural and functional conservation of the few universally distributed proteins that were undoubtedly present in the last common ancestor and that carry out membrane-associated functions. These include the SecY subunit of the protein-conducting channel, the signal recognition particle, the signal recognition particle receptor, the signal peptidase, and the proton ATPase. The conserved structural and functional aspects of these proteins indicate that the last common ancestor was associated with a hydrophobic layer with two hydrophilic sides (an inside and an outside) that had a full-fledged and asymmetric protein insertion and translocation machinery and served as a permeability barrier for protons and other small molecules. It is difficult to escape the conclusion that the last common ancestor had a closed biological membrane from which all cellular membranes evolved.
Abstract.
Author URL.
Jékely G, Arendt D (2006). Evolution of intraflagellar transport from coated vesicles and autogenous origin of the eukaryotic cilium.
Bioessays,
28(2), 191-198.
Abstract:
Evolution of intraflagellar transport from coated vesicles and autogenous origin of the eukaryotic cilium.
The cilium/flagellum is a sensory-motile organelle ancestrally present in eukaryotic cells. For assembly cilia universally rely on intraflagellar transport (IFT), a specialised bidirectional transport process mediated by the ancestral and conserved IFT complex. Based on the homology of IFT complex proteins to components of coat protein I (COPI) and clathrin-coated vesicles, we propose that the non- vesicular, membrane-bound IFT evolved as a specialised form of coated vesicle transport from a protocoatomer complex. IFT thus shares common ancestry with all protocoatomer derivatives, including all vesicle coats and the nuclear pore complex (NPC). This has major implications for the evolutionary origin of the cilium. First, it reinforces the tenet that duplication and divergence of pre-existing structures, rather than symbiosis, were the major themes during cilium evolution. Second, it suggests that the initial step in the autogenous origin of the cilium was the establishment of a membrane patch with transmembrane proteins transported by the ancestral vesicle-coating IFT complex. We propose a scenario for how the initial membrane patch gradually protruded to enhance exposure to the environment, then started to move, and finally compartmentalised to render receptor signalling and ciliary beating more efficient.
Abstract.
Author URL.
2005
Fritzsch B, Piatigorsky J, Tessmar-Raible K, Jékely G, Guy K, Raible F, Wittbrodt J, Arendt D (2005). Ancestry of Photic and Mechanic Sensation?.
Science,
308(5725), 1113-1114.
Author URL.
Tessmar-Raible K, Jekely G, Guy K, Raible F, Wittbrodt J, Arendt D (2005). Ancestry of photic and mechanic sensation? Response.
SCIENCE,
308(5725), 1114-1114.
Author URL.
Jékely G (2005). Glimpsing over the event horizon: evolution of nuclear pores and envelope.
Cell Cycle,
4(2), 297-299.
Abstract:
Glimpsing over the event horizon: evolution of nuclear pores and envelope.
The origin of eukaryotes from prokaryotic ancestors is one of the major evolutionary transitions in the history of life. The nucleus, a membrane bound compartment for confining the genome, is a central feature of eukaryotic cells and its origin also has to be a central feature of any workable theory that ventures to explain eukaryotic origins. Recent bioinformatic analyses of components of the nuclear pore complex (NPC), the nuclear envelope (NE), and the nuclear transport systems revealed exciting evolutionary connections (e.g. between NPC and coated vesicles) and provided a useful record of the phyletic distribution and history of NPC and NE components. These analyses allow us to refine theories on the origin and evolution of the nucleus, and consequently, of the eukaryotic cell.
Abstract.
Author URL.
Jékely G (2005). Least of all visible things. FEBS Letters, 579(15).
Jékely G, Sung H-H, Luque CM, Rørth P (2005). Regulators of endocytosis maintain localized receptor tyrosine kinase signaling in guided migration.
Dev Cell,
9(2), 197-207.
Abstract:
Regulators of endocytosis maintain localized receptor tyrosine kinase signaling in guided migration.
Guidance receptors detect extracellular cues and instruct migrating cells how to orient in space. Border cells perform a directional invasive migration during Drosophila oogenesis and use two receptor tyrosine kinases (RTKs), EGFR and PVR (PDGF/VEGF Receptor), to read guidance cues. We find that spatial localization of RTK signaling within these migrating cells is actively controlled. Border cells lacking Cbl, an RTK-associated E3 ubiquitin ligase, have delocalized guidance signaling, resulting in severe migration defects. Absence of Sprint, a receptor-recruited, Ras-activated Rab5 guanine exchange factor, gives related defects. In contrast, increasing the level of RTK signaling by receptor overexpression or removing Hrs and thereby decreasing RTK degradation does not perturb migration. Cbl and Sprint both regulate early steps of RTK endocytosis. Thus, a physiological role of RTK endocytosis is to ensure localized intracellular response to guidance cues by stimulating spatial restriction of signaling.
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Author URL.
2004
Farkas A, Tompa P, Schád E, Sinka R, Jékely G, Friedrich P (2004). Autolytic activation and localization in Schneider cells (S2) of calpain B from Drosophila.
Biochem J,
378(Pt 2), 299-305.
Abstract:
Autolytic activation and localization in Schneider cells (S2) of calpain B from Drosophila.
Calpain B is one of the two calpain homologues in Drosophila melanogaster that are proteolytically active. We studied its activation by Ca2+ both in vitro and in vivo, in Schneider (S2) cells. Activation involves the autolytic cleavage, at two major sites, of the N-terminal segment, the length of which was earlier underestimated. Site-directed mutagenesis at the autolytic sites did not prevent autolysis, but only shifted its sites. Calpain B mRNA was detectable in all developmental stages of the fly. In situ hybridization and immunostaining showed expression in ovaries, embryo and larvae, with high abundance in larval salivary glands. In S2 cells, calpain B was mainly in the cytoplasm and upon a rise in Ca2+ the enzyme adhered to intracellular membranes.
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Author URL.
2003
Jékely G, Rørth P (2003). Hrs mediates downregulation of multiple signalling receptors in Drosophila.
EMBO Rep,
4(12), 1163-1168.
Abstract:
Hrs mediates downregulation of multiple signalling receptors in Drosophila.
Endocytosis and subsequent lysosomal degradation of activated signalling receptors can attenuate signalling. Endocytosis may also promote signalling by targeting receptors to specific compartments. A key step regulating the degradation of receptors is their ubiquitination. Hrs/Vps27p, an endosome-associated, ubiquitin-binding protein, affects sorting and degradation of receptors. Drosophila embryos mutant for hrs show elevated receptor tyrosine kinase (RTK) signalling. Hrs has also been proposed to act as a positive mediator of TGF-beta signalling. We find that Drosophila epithelial cells devoid of Hrs accumulate multiple signalling receptors in an endosomal compartment with high levels of ubiquitinated proteins: not only RTKs (EGFR and PVR) but also Notch and receptors for Hedgehog and Dpp (TGF-beta related). Hrs is not required for Dpp signalling. Instead, loss of Hrs increases Dpp signalling and the level of the type-I receptor Thickveins (Tkv). Finally, most hrs-dependent receptor turnover appears to be ligand independent. Thus, both active and inactive signalling receptors are targeted for degradation in vivo and Hrs is required for their removal.
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Author URL.
Jékely G (2003). Small GTPases and the evolution of the eukaryotic cell.
Bioessays,
25(11), 1129-1138.
Abstract:
Small GTPases and the evolution of the eukaryotic cell.
The origin of eukaryotes is one of the major challenges of evolutionary cell biology. Other than the endosymbiotic origin of mitochondria and chloroplasts, the steps leading to eukaryotic endomembranes and endoskeleton are poorly understood. Ras-family small GTPases are key regulators of cytoskeleton dynamics, vesicular trafficking and nuclear function. They are specific for eukaryotes and their expansion probably traces the evolution of core eukaryote features. The phylogeny of small GTPases suggests that the first endomembranes to evolve during eukaryote evolution had secretory, and not phagocytic, function. Based on the reconstruction of putative roles for ancestral small GTPases, a hypothetical scenario on the origins of the first endomembranes, the nucleus, and phagocytosis is presented.
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Author URL.
2002
Schád E, Farkas A, J́ekely G, Tompa P, Friedrich P (2002). A novel human small subunit of calpains.
Biochemical Journal,
362(2), 383-388.
Abstract:
A novel human small subunit of calpains
Typical calpains are heterodimeric cysteine proteases which have distinct large catalytic subunits (80 kDa) but share a common small regulatory subunit (30 kDa; css1). Here we report the identification, cloning and characterization of a novel human small subunit (css2) encoded by an intronless gene, capns2, located on chromosome 16. This new protein displays 73% sequence identity within the Ca2+-binding region but lacks two oligo-Gly stretches characteristic of the N-terminal domain of the conventional small subunit. css2 appears to be the functional equivalent of the conventional small subunit in vitro in that it helps the large subunit fold into the active conformation of similar Ca2+ sensitivity when the two proteins are co-expressed in Escherichia coli. The purification of various chimaeric rat 80 kDa-human css2 constructs, on the other hand, shows that css2 binds the large subunit much more weakly than css1. Further, it does not undergo the autolytic conversion typical of the classical small subunit. The expression of this protein in vivo, as assessed from its appearance in expressed sequence tag clones, is rather limited, making it an example of a tissue-specific, rather than ubiquitous, small subunit.
Abstract.
Jékely G (2002). Evolution in a nutshell. EMBL PhD student symposium on evolution.
EMBO Rep,
3(4), 307-311.
Author URL.
Jekely G (2002). The human genome sequence. A triumph of chemistry: If the history of molecular biology is written in the future, the first chapter should be devoted to the chemists who did the ground work.
EMBO Rep,
3(7), 594-595.
Author URL.
2001
Friedrich P, Tompa P, Jekely G, Farkas A, Schad T (2001). Calpains in cellular signalling.
Author URL.
Szabó K, Jékely G, Rørth P (2001). Cloning and expression of sprint, a Drosophila homologue of RIN1.
Mech Dev,
101(1-2), 259-262.
Abstract:
Cloning and expression of sprint, a Drosophila homologue of RIN1.
The small GTPase Ras is critical for regulation of growth and differentiation during development. The mammalian protein RIN1 is a potential Ras effector protein, which can also interact with the Abelson tyrosine kinase. However, its biological function is unknown. We have identified the Drosophila homologue of RIN1, called sprint, for SH2, poly-proline containing Ras interactor. The sprint locus is very large and contains at least two differentially expressed isoforms (sprint-a and sprint-b). Both isoforms are expressed in the ovary and maternal mRNA is deposited into embryos. In addition, sprint is zygotically expressed in the developing midgut, amnioserosa and in a specific subset of CNS neurons. The expression patterns of the two sprint isoforms are temporally distinct suggesting that the isoforms may have unique functions.
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Author URL.
Duchek P, Somogyi K, Jékely G, Beccari S, Rørth P (2001). Guidance of cell migration by the Drosophila PDGF/VEGF receptor.
Cell,
107(1), 17-26.
Abstract:
Guidance of cell migration by the Drosophila PDGF/VEGF receptor.
Directed cell migrations are important for development, but the signaling pathways and mechanisms responsible for guiding cell migration in vivo are poorly understood. Migration of border cells during Drosophila oogenesis is a simple and attractive model system in which to address these questions. We demonstrate that PVR, a receptor tyrosine kinase related to mammalian PDGF and VEGF receptors, acts in border cells to guide them to the oocyte. The oocyte is the source of a ligand for PVR, PDGF/VEGF factor 1 (PVF1). Intriguingly, the guidance function of PVR is largely redundant with that of EGFR. We present evidence implicating Rac and the Rac activator Mbc/DOCK180/CED-5 as mediators of the guidance signal.
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Author URL.
2000
Jékely G, Pintér M, Friedrich P (2000). Drosophila calpains. Purification of a calpain-like enzyme from fruit flies, and expression in Escherichia coli.
Methods Mol Biol,
144, 67-74.
Author URL.
1999
Jékely G, Friedrich P (1999). Characterization of two recombinant Drosophila calpains. CALPA and a novel homolog, CALPB.
J Biol Chem,
274(34), 23893-23900.
Abstract:
Characterization of two recombinant Drosophila calpains. CALPA and a novel homolog, CALPB.
We have sequenced the cDNA of a novel Ca(2+)-activated cysteine proteinase (calpain) from the fruit fly, Drosophila melanogaster. The predicted protein, designated as CALPB, shows high similarity to the previously identified Drosophila calpain, CALPA. The two proteins were expressed in Escherichia coli and purified to homogeneity by metal-chelate affinity chromatography either from inclusion bodies or from the bacterial cytosol. Both enzymes were Ca(2+)-dependent proteinases and attained half-maximal activation in the presence of millimolar Ca(2+). The activity and the rate of activation of CALPA, but not CALPB, could be activated by phosphatidylinositol 4,5-diphosphate, phosphatidylinositol 4-monophosphate, phosphatidylinositol, and phosphatidic acid. A truncated form of CALPA, lacking the CALPA-specific unique insertion region, has also been expressed and characterized. Although it lacked the 16-amino acid long putative membrane-anchoring segment, its activation by phospholipids was similar to that of the full-length CALPA protein. The enzymes undergo N-terminal autolysis in a Ca(2+)-dependent manner which was shown with CALPB to run parallel with enzyme activation. Moreover, fully autolyzed CALPB lacked the characteristic activation phase indicating the requirement for autolysis upon activation of this calpain form in vitro. The analysis of the mechanism of activation in Drosophila calpains seems to corroborate the autolysis model of calpain activation.
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Author URL.
Jékely G, Friedrich P (1999). The evolution of the calpain family as reflected in paralogous chromosome regions.
J Mol Evol,
49(2), 272-281.
Abstract:
The evolution of the calpain family as reflected in paralogous chromosome regions.
Calpains, the Ca(2+)-dependent intracellular proteinases, are involved in the regulation of distinct cellular pathways including signal transduction and processing, cytoskeleton dynamics, and muscle homeostasis. To investigate the evolutionary origin of diverse calpain subfamilies, a phylogenetic study was carried out. The topology of the calpain phylogenetic tree has shown that some of the gene duplications occurred before the divergence of the protostome and deuterostome lineages. Other gene doublings, leading to vertebrate-specific calpain forms, took place during early chordate evolution and coincided with genome duplications as disclosed by the localization of calpain genes to paralogous chromosome regions in the human genome. On the basis of the phylogenetic tree, the time of gene duplications, and the localization of calpain genes, we propose a model of tandem and chromosome duplications for the evolution of vertebrate-specific calpain forms. The data presented here are consistent with scenarios proposed for the evolution of other multigene families.
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1998
Pintér M, Jékely G, Szepesi RJ, Farkas A, Theopold U, Meyer HE, Lindholm D, Nässel DR, Hultmark D, Friedrich P, et al (1998). TER94, a Drosophila homolog of the membrane fusion protein CDC48/p97, is accumulated in nonproliferating cells: in the reproductive organs and in the brain of the imago.
Insect Biochem Mol Biol,
28(2), 91-98.
Abstract:
TER94, a Drosophila homolog of the membrane fusion protein CDC48/p97, is accumulated in nonproliferating cells: in the reproductive organs and in the brain of the imago.
We have cloned a Drosophila homolog of the membrane fusion protein CDC48/p97. The open reading frame of the Drosophila homolog encodes an 801 amino acid long protein (TER94), which shows high similarity to the known CDC48/p97 sequences. The chromosomal position of TER94 is 46 C/D. TER94 is expressed in embryo, in pupae and in imago, but is suppressed in larva. In the imago, the immunoreactivity was exclusively present in the head and in the gonads of both sexes. In the head the most striking staining was observed in the entire neuropil of the mushroom body and in the antennal glomeruli. Besides TER94, sex-specific forms were also detected in the gonads of the imago: p47 in the ovaries and p98 in the testis. TER94/p47 staining was observed in the nurse cells and often in the oöcytes, while TER94/p98 staining was present in the sperm bundles. On the basis of its distribution we suggest that TER94 functions in the protein transport utilizing endoplasmic reticulum and Golgi derived vesicles.
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