IBCS seminar - Steffen Scholpp (Exeter University)

Cytonemes regulate wnt transport in development and disease

An Institute of Biomedical and Clinical Science seminar
Date	24 November 2021
Time	15:00 to 16:30
Place	Zoom - https://Universityofexeter.zoom.us/j/98780355173?pwd=d3IyaUQ0NlN2TWVWMEpCc3Y2TFE1dz09

IBCS seminar hosted by Professor Soojin Ryu

Bio:
Dr Steffen Scholpp is an associate professor for cell and developmental biology and studies cell-cell communication in zebrafish, cancer and neuronal tissue. He focuses on cell biological mechanisms regulating the distribution and function of signalling molecules in development and tissue homeostasis. By using fluorescently tagged Wnt ligands, he was able to describe for the first time the dynamic spreading of Wnt on signalling filopodia between cells in real-time. Based on these findings, he investigates the underlying molecular mechanism of the emergence of these Wnt cytonemes in zebrafish embryogenesis and gastric cancer. Cytonemal transport of signalling proteins is now considered so fundamental that his work appears in a dedicated chapter in Scott Gilbert's textbook ''Developmental Biology''. With support from BBSRC equipment grants, he has expanded the quantitative imaging technologies at UoE, such as fluorescence correlation spectroscopy and lattice SIM. He also has active collaborations with AstraZeneca using zebrafish as a model to identify drug targets and with the microscopy company Leica Microsystems to develop and adapt new quantitative imaging technologies for in vivo applications. In conclusion, SS has 18 years of experience in analysing morphogen signalling in model organisms with over 45 publications, h-index 30, over 3,100 citations. MRC, BBSRC, and the Alzheimer's charity BRACE support his research.

Abstract

Abstract:
After secretion, developmental signals known as morphogens must travel distances to form a concentration gradient that the responding tissue uses to acquire positional information. The role of morphogen transport in this process is the subject of intense debate. Wnt proteins regulate developmental processes, tissue regeneration and stem cell maintenance. It has been postulated that Wnt/beta-catenin signalling forms concentration gradients across responsive tissues and act as morphogens. However, little is known about the transport mechanism for these lipid-modified signalling proteins in vertebrates.

Here we show that Wnt8a proteins are transported on short, actin-based filopodia known as cytonemes to contact responding cells and activate signalling in zebrafish embryogenesis. We further demonstrate that the transmembrane protein Vangl2, in concert with the receptor Ror2, activates the beta-catenin independent PCP pathway to regulate the formation of cytonemes. Finally, we show that PCP signalling in the Wnt producing cells controls the effective signalling range of Wnt in zebrafish embryos. We further demonstrate that gastric cancer cells utilise cytonemes to transport Wnt3 intercellularly to promote proliferation. Furthermore, we identify the membrane-bound scaffolding protein Flot2, frequently overexpressed in gastric cancer, as a regulator of these cytonemes. Together with the Wnt co-receptor and cytoneme regulator Ror2, Flot2 determines the number and length of Wnt3 cytonemes in gastric cancer. We conclude that cytoneme-based trafficking is fundamental for Wnt signalling in development and disease.

Link to seminar - https://Universityofexeter.zoom.us/j/98780355173?pwd=d3IyaUQ0NlN2TWVWMEpCc3Y2TFE1dz09

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