roundabout4 is essential for angiogenesis in vivo.
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.
Bedell
Victoria M
VM
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, 9610 Medical Center Drive, Suite 320, Rockville, MD 20850, USA.
Yeo
Sang-Yeob
SY
Park
Kye Won
KW
Chung
Jeffrey
J
Seth
Pankaj
P
Shivalingappa
Venkatesha
V
Zhao
Jinhua
J
Obara
Tomoko
T
Sukhatme
Vikas P
VP
Drummond
Iain A
IA
Li
Dean Y
DY
Ramchandran
Ramani
R
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D019295:Computational Biology; D017931:DNA Primers; D004727:Endothelium / Q000502:physiology; D015870:Gene Expression; D005816:Genetic Complementation Test; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000235:genetics* / Q000502:physiology; D009841:Oligonucleotides; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017385:Sequence Homology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D000097905:Roundabout Proteins
D017931:DNA Primers; D009841:Oligonucleotides; D011956:Receptors, Cell Surface; D029961:Zebrafish Proteins; C502398:ROBO4 protein, zebrafish; D000097905:Roundabout Proteins