Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/β-catenin pathway during brain angiogenesis
| Title: | Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/β-catenin pathway during brain angiogenesis |
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| Authors: | Benoit Vanhollebeke, Oliver A Stone, Naguissa Bostaille, Chris Cho, Yulian Zhou, Emilie Maquet, Anne Gauquier, Pauline Cabochette, Shigetomo Fukuhara, Naoki Mochizuki, Jeremy Nathans, Didier YR Stainier |
| Source: | eLife, Vol 4 (2015) |
| Publisher Information: | eLife Sciences Publications Ltd, 2015. |
| Publication Year: | 2015 |
| Collection: | LCC:Medicine LCC:Science LCC:Biology (General) |
| Subject Terms: | brain vascular development, tip cell, angiogenesis, Reck, Gpr124, Wnt7a/Wnt7b, Medicine, Science, Biology (General), QH301-705.5 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2050-084X |
| Relation: | https://elifesciences.org/articles/06489; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.06489 |
| Access URL: | https://doaj.org/article/0e768fb1794c4364b3e28435ee224987 |
| Accession Number: | edsdoj.0e768fb1794c4364b3e28435ee224987 |
| Database: | Directory of Open Access Journals |
| ISSN: | 2050084X |
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| DOI: | 10.7554/eLife.06489 |
| Published in: | eLife |
| Language: | English |