title: roundabout4 is essential for angiogenesis in vivo.
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.
authors.affiliation: Laboratory of Pathology, National Cancer Institute, National Institutes of Health, 9610 Medical Center Drive, Suite 320, Rockville, MD 20850, USA.
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Bedell
authors.forename: Sang-Yeob
authors.initials: SY
authors.lastname: Yeo
authors.forename: Kye Won
authors.initials: KW
authors.lastname: Park
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Chung
authors.forename: Pankaj
authors.initials: P
authors.lastname: Seth
authors.forename: Venkatesha
authors.initials: V
authors.lastname: Shivalingappa
authors.forename: Jinhua
authors.initials: J
authors.lastname: Zhao
authors.forename: Tomoko
authors.initials: T
authors.lastname: Obara
authors.forename: Vikas P
authors.initials: VP
authors.lastname: Sukhatme
authors.forename: Iain A
authors.initials: IA
authors.lastname: Drummond
authors.forename: Dean Y
authors.initials: DY
authors.lastname: Li
authors.forename: Ramani
authors.initials: R
authors.lastname: Ramchandran
mesh_terms: 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
chemical_list: D017931:DNA Primers; D009841:Oligonucleotides; D011956:Receptors, Cell Surface; D029961:Zebrafish Proteins; C502398:ROBO4 protein, zebrafish; D000097905:Roundabout Proteins