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Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/β-catenin pathway during brain angiogenesis
- Source :
- eLife, eLife, 4, eLife, Vol 4 (2015)
- Publication Year :
- 2015
-
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.<br />SCOPUS: ar.j<br />info:eu-repo/semantics/published
- Subjects :
- Angiogenesis
Fluorescent Antibody Technique
Blood vessel morphogenesis
Polymerase Chain Reaction
Receptors, G-Protein-Coupled
Animals, Genetically Modified
angiogenesis
0302 clinical medicine
Ganglia, Spinal
Immunologie
Morphogenesis
brain vascular development
Biology (General)
Luciferases
Zebrafish
Wnt Signaling Pathway
In Situ Hybridization
0303 health sciences
Microscopy, Confocal
General Neuroscience
Neurogenesis
Wnt signaling pathway
Brain
General Medicine
Sciences bio-médicales et agricoles
Cell biology
Medicine
Signal transduction
Single-Cell Analysis
Research Article
QH301-705.5
Science
Neovascularization, Physiologic
Biology
GPI-Linked Proteins
Time-Lapse Imaging
Gpr124
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Animals
Wnt7a/Wnt7b
030304 developmental biology
DNA Primers
Analysis of Variance
General Immunology and Microbiology
Neurosciences cognitives
tip cell
Zebrafish Proteins
biology.organism_classification
Microarray Analysis
WNT7A
Developmental Biology and Stem Cells
Mutagenesis
Catenin
Microbiologie et protistologie [bacteriol.virolog.mycolog.]
Reck
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 2050084X
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- eLife
- Accession number :
- edsair.doi.dedup.....0719d349e62d30b706690a40d9b7f4e2