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

Microscopy, Confocal
Polymerase Chain Reaction
In Situ Hybridization
Brain/blood supply*
Brain/embryology
Morphogenesis/physiology*
DNA Primers/genetics
Time-Lapse Imaging
Fluorescent Antibody Technique
Wnt Signaling Pathway/physiology*
Neovascularization, Physiologic/physiology*
Zebrafish Proteins/metabolism*
Mutagenesis
GPI-Linked Proteins/metabolism*
Microarray Analysis
Analysis of Variance
Animals
Zebrafish/embryology*
Receptors, G-Protein-Coupled/metabolism*
Animals, Genetically Modified
Single-Cell Analysis
Ganglia, Spinal/physiology
Luciferases
Neurogenesis/physiology

(all 24)

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