ZFIN ID: ZDB-PUB-150609-10
Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/β-catenin pathway during brain angiogenesis
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.
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
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.