Wnt is ancient pathway, whose evolutionary appearance dates back to the emergence of multicellular animals. It plays pivotal roles in cell to cell communication and governs several aspects of embryonic development and tissue homeostasis. When dysfunctional, Wnt signaling can be at the origin of many diseases, in particular several cancers. With 10 receptors and 19 ligands, recognizing each other, the complexity of the pathway seemed dizzying. How do vertebrate cells manage to interpret the many Wnt signals they encounter and trigger an adequate response? It is such an interpretation mechanism that ULB researchers have just discovered.
Previous findings had shown that two proteins expressed by cerebral endothelial cells, Gpr124 and Reck, are required for cerebrovascular development in response Wnt7 ligands. The team went on to study the mechanism by which the complex operates. Using genetic, biophysical and zebrafish experiments, researchers have shown that the complex Gpr124 / Reck acts as a decoding module: Reck recognizes the Wnt7 ligand, but the presence of Gpr124 is necessary to trigger Wnt7 signaling via Frizzled receptors. Their results are detailed in Science. Paper. (paywall) – Marie Eubelen, Naguissa Bostaille, Pauline Cabochette, Anne Gauquier, Patricia Tebabi, Andra C. Dumitru, Melanie Koehler, Philipp Gut, David Alsteens, Didier Y. R. Stainier, Abel Garcia-Pino, Benoit Vanhollebeke. A molecular mechanism for Wnt ligand-specific signaling. Science, 2018; eaat1178 DOI: 10.1126/science.aat1178 More.
Presumably, it was easy for all this signalling to just somehow fall into place once, a long time ago …
One approach with an excellent track record is: Make expressions of doubt dangerous. That stops the problem from becoming visibly worse even while it mounts.
See also: At Science: Maybe the transition from single cells to multicellular life wasn’t that hard? So at the basic level, there is a program that adapts single cells to multicellularity? Yes, that certainly makes multicellularity easier and even swifter but it also make traditional Darwinian explanations sound ever more stretched.