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Development. 2016 Jan 1;143(1):147-59. doi: 10.1242/dev.123059. Epub 2015 Dec 10.

Reck enables cerebrovascular development by promoting canonical Wnt signaling.

Author information

1
Dept of Cell Biology, Skirball Institute of Biomolecular Medicine, NYU Langone Medical Center, 540 First Avenue, New York, NY 10016, USA.
2
Program in Genomics of Differentiation, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
3
Department of Biological Structure, University of Washington, Seattle, WA 98195, USA.
4
Stony Brook University, Stony Brook, NY 11794, USA.
5
Dept of Cell Biology, Skirball Institute of Biomolecular Medicine, NYU Langone Medical Center, 540 First Avenue, New York, NY 10016, USA torres@saturn.med.nyu.edu.

Abstract

The cerebral vasculature provides the massive blood supply that the brain needs to grow and survive. By acquiring distinctive cellular and molecular characteristics it becomes the blood-brain barrier (BBB), a selectively permeable and protective interface between the brain and the peripheral circulation that maintains the extracellular milieu permissive for neuronal activity. Accordingly, there is great interest in uncovering the mechanisms that modulate the formation and differentiation of the brain vasculature. By performing a forward genetic screen in zebrafish we isolated no food for thought (nft (y72)), a recessive late-lethal mutant that lacks most of the intracerebral central arteries (CtAs), but not other brain blood vessels. We found that the cerebral vascularization deficit of nft (y72) mutants is caused by an inactivating lesion in reversion-inducing cysteine-rich protein with Kazal motifs [reck; also known as suppressor of tumorigenicity 15 protein (ST15)], which encodes a membrane-anchored tumor suppressor glycoprotein. Our findings highlight Reck as a novel and pivotal modulator of the canonical Wnt signaling pathway that acts in endothelial cells to enable intracerebral vascularization and proper expression of molecular markers associated with BBB formation. Additional studies with cultured endothelial cells suggest that, in other contexts, Reck impacts vascular biology via the vascular endothelial growth factor (VEGF) cascade. Together, our findings have broad implications for both vascular and cancer biology.

KEYWORDS:

Angiogenesis; Blood-brain barrier; Brain vasculature; Reck; VEGF; Wnt

PMID:
26657775
PMCID:
PMC4725199
DOI:
10.1242/dev.123059
[Indexed for MEDLINE]
Free PMC Article

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