par Vanhollebeke, Benoît
;Stone, Oliver A;Bostaille, Naguissa
;Cho, Chris;Zhou, Yulian;Maquet, Emilie
;Gauquier, Anne
;Cabochette, Pauline
;Fukuhara, Shigetomo;Mochizuki, Naoki;Nathans, Jeremy;Stainier, Didier Y R
Référence eLife, 4, page (1-25), e06489
Publication Publié, 2015-06





Référence eLife, 4, page (1-25), e06489
Publication Publié, 2015-06
Article révisé par les pairs
Résumé : | Despite the critical role of endothelial Wnt/β-catenin signaling during central nervous system (CNS) vascularization, how endothelial cells sense and respond to specific Wnt ligands and what aspects of the multistep process of intra-cerebral blood vessel morphogenesis are controlled by these angiogenic signals remain poorly understood. We addressed these questions at single-cell resolution in zebrafish embryos. We identify the GPI-anchored MMP inhibitor Reck and the adhesion GPCR Gpr124 as integral components of a Wnt7a/Wnt7b-specific signaling complex required for brain angiogenesis and dorsal root ganglia neurogenesis. We further show that this atypical Wnt/ β-catenin signaling pathway selectively controls endothelial tip cell function and hence, that mosaic restoration of single wild-type tip cells in Wnt/β-catenin-deficient perineural vessels is sufficient to initiate the formation of CNS vessels. Our results identify molecular determinants of ligand specificity of Wnt/β-catenin signaling and provide evidence for organ-specific control of vascular invasion through tight modulation of tip cell function. |