PAPC couples the Segmentation Clock to somite morphogenesis by regulating N-cadherindependent adhesion

International audienceVertebrate segmentation is characterized by the periodic formation of epithelialsomites from the mesenchymal presomitic mesoderm (PSM). How the rhythmicsignaling pulse delivered by the Segmentation Clock is translated into theperiodic morphogenesis of somites remains poorly understood. Here, we focusedon the role of Paraxial protocadherin (PAPC/Pcdh8) in this process. We showedthat in chicken and mouse embryos, PAPC expression is tightly regulated by theClock and Wavefront system in the posterior PSM. We observed that PAPCexhibits a striking complementary pattern to N-Cadherin (CDH2), marking theinterface of the future somite boundary in the anterior PSM. Gain and loss offunction of PAPC in chicken embryos disrupt somite segmentation by altering theCDH2-dependent epithelialization of PSM cells. Our data suggest that clathrin mediatedendocytosis is increased in PAPC expressing cells, subsequentlyaffecting CDH2 internalization in the anterior compartment of the future somite.This in turn generates a differential adhesion interface, allowing formation of theacellular fissure that defines the somite boundary. Thus periodic expression ofPAPC in the anterior PSM triggers rhythmic endocytosis of CDH2, allowing forsegmental de-adhesion and individualization of somites