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roundabout4 is essential for angiogenesis in vivo

2005; National Academy of Sciences; Volume: 102; Issue: 18 Linguagem: Inglês

10.1073/pnas.0408318102

1091-6490

Victoria M. Bedell, Sang‐Yeob Yeo, Kye Won Park, Jeffrey W. Chung, Pankaj Seth, Shivalingappa Venkatesha, Jinhua Zhao, Tomoko Obara, Vikas P. Sukhatme, Iain A. Drummond, Dean Y. Li, Ramani Ramchandran,

Angiogenesis and VEGF in Cancer

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 .