PUBLICATION
Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/?-catenin pathway during brain angiogenesis
- Authors
- Vanhollebeke, B., Stone, O.A., Bostaille, N., Cho, C., Zhou, Y., Maquet, E., Gauquier, A., Cabochette, P., Fukuhara, S., Mochizuki, N., Nathans, J., Stainier, D.Y.
- ID
- ZDB-PUB-150609-10
- Date
- 2015
- Source
- eLIFE 4: (Journal)
- Registered Authors
- Fukuhara, Shigetomo, Mochizuki, Naoki, Stainier, Didier, Vanhollebeke, Benoit
- Keywords
- Gpr124, Reck, Wnt7a/Wnt7b, angiogenesis, brain vascular development, developmental biology, stem cells, tip cell, zebrafish
- MeSH Terms
-
- Polymerase Chain Reaction
- Mutagenesis
- Single-Cell Analysis
- Analysis of Variance
- Morphogenesis/physiology*
- Wnt Signaling Pathway/physiology*
- Animals
- Zebrafish/embryology*
- Animals, Genetically Modified
- Microscopy, Confocal
- DNA Primers/genetics
- Ganglia, Spinal/physiology
- Brain/blood supply*
- Brain/embryology
- Time-Lapse Imaging
- Fluorescent Antibody Technique
- Zebrafish Proteins/metabolism*
- In Situ Hybridization
- GPI-Linked Proteins/metabolism*
- Neovascularization, Physiologic/physiology*
- Receptors, G-Protein-Coupled/metabolism*
- Microarray Analysis
- Luciferases
- Neurogenesis/physiology
- PubMed
- 26051822 Full text @ Elife
Citation
Vanhollebeke, B., Stone, O.A., Bostaille, N., Cho, C., Zhou, Y., Maquet, E., Gauquier, A., Cabochette, P., Fukuhara, S., Mochizuki, N., Nathans, J., Stainier, D.Y. (2015) Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/?-catenin pathway during brain angiogenesis. eLIFE. 4.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping