Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/β-catenin pathway during brain angiogenesis

Benoit Vanhollebeke, Oliver A. Stone, Naguissa Bostaille, Chris Cho, Yulian Zhou, Emilie Maquet, Anne Gauquier, Pauline Cabochette, Shigetomo Fukuhara, Naoki Mochizuki, Jeremy Nathans, Didier Y.R. Stainier

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere06489
Pages (from-to)1-25
Number of pages25
JournaleLife
Volume4
Issue numberJUNE
DOIs
StatePublished - Jun 8 2015

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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