Reference - Detail
| RRC ID | 82780 |
|---|---|
| Author | Vanhollebeke B, Stone OA, Bostaille N, Cho C, Zhou Y, Maquet E, Gauquier A, Cabochette P, Fukuhara S, Mochizuki N, Nathans J, Stainier DY. |
| Title | Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/β-catenin pathway during brain angiogenesis. |
| Journal | Elife |
| Abstract |
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. |
| Volume | 4 |
| Published | 2015-6-8 |
| DOI | 10.7554/eLife.06489 |
| PMID | 26051822 |
| PMC | PMC4456509 |
| MeSH | Analysis of Variance Animals Animals, Genetically Modified Brain / blood supply* Brain / embryology DNA Primers / genetics Fluorescent Antibody Technique GPI-Linked Proteins / metabolism* Ganglia, Spinal / physiology In Situ Hybridization Luciferases Microarray Analysis Microscopy, Confocal Morphogenesis / physiology* Mutagenesis Neovascularization, Physiologic / physiology* Neurogenesis / physiology Polymerase Chain Reaction Receptors, G-Protein-Coupled / metabolism* Single-Cell Analysis Time-Lapse Imaging Wnt Signaling Pathway / physiology* Zebrafish / embryology* Zebrafish Proteins / metabolism* |
| IF | 7.08 |
| Resource | |
| Zebrafish | UAS:GFP |