PUBLICATION

Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/β-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
  • 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*
PubMed
26051822 Full text @ 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.
Genes / Markers
Figures
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping