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Proc Natl Acad Sci U S A. 2005 May 3;102(18):6373-8. Epub 2005 Apr 22.

roundabout4 is essential for angiogenesis in vivo.

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1
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, 9610 Medical Center Drive, Suite 320, Rockville, MD 20850, USA.

Abstract

Stereotypical patterns of vascular and neuronal networks suggest that specific genetic programs tightly control path determination and, consequently, angiogenesis and axon-guidance mechanisms. Our study focuses on one member of the roundabout family of receptors, which traditionally mediate repulsion from the midline. Here, we characterize a fourth member of this family, roundabout4 (robo4), which is the predominant roundabout (robo) that is expressed in embryonic zebrafish vasculature. Gene knockdown and overexpression approaches show that robo4 is essential for coordinated symmetric and directed sprouting of intersomitic vessels and provide mechanistic insights into this process. Also, human robo4 gene functionally compensates for loss of robo4 gene function, suggesting evolutionary conservation. This article reports an endothelial-specific function for a robo gene in vertebrates in vivo.

PMID:
15849270
PMCID:
PMC1088354
DOI:
10.1073/pnas.0408318102
[Indexed for MEDLINE]
Free PMC Article
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