IBCS seminar - Steffen Scholpp (Exeter University)

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