TY - JOUR TI - Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/β-catenin pathway during brain angiogenesis AU - Vanhollebeke, Benoit AU - Stone, Oliver A AU - Bostaille, Naguissa AU - Cho, Chris AU - Zhou, Yulian AU - Maquet, Emilie AU - Gauquier, Anne AU - Cabochette, Pauline AU - Fukuhara, Shigetomo AU - Mochizuki, Naoki AU - Nathans, Jeremy AU - Stainier, Didier YR A2 - Rossant, Janet VL - 4 PY - 2015 DA - 2015/06/08 SP - e06489 C1 - eLife 2015;4:e06489 DO - 10.7554/eLife.06489 UR - https://doi.org/10.7554/eLife.06489 AB - 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. KW - brain vascular development KW - tip cell KW - angiogenesis KW - Reck KW - Gpr124 KW - Wnt7a/Wnt7b JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -