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 repulsio...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-05, Vol.102 (18), p.6373-6378
Main Authors: Bedell, Victoria M., Yeo, Sang-Yeob, Park, Kye Won, Chung, Jeffrey, Seth, Pankaj, Shivalingappa, Venkatesha, Zhao, Jinhua, Obara, Tomoko, Sukhatme, Vikas P., Drummond, Iain A., Li, Dean Y., Ramchandran, Ramani, Anderson, Kathryn V.
Format: Article
Language:English
Subjects:
Angiogenesis
Animals
Base Sequence
Biological Sciences
Cardiovascular system
Cloning, Molecular
Computational Biology
Danio rerio
DNA Primers
Embryos
Endothelial cells
Endothelium - physiology
Exons
Fish
Gels
Gene Expression
Genetic Complementation Test
Genetics
Immunohistochemistry
In Situ Hybridization
Ligands
Molecular Sequence Data
Neovascularization, Physiologic - genetics
Neovascularization, Physiologic - physiology
Neurons
Oligonucleotides
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
RNA
Sequence Homology
Sprouting
Sprouts
Zebrafish - embryology
Zebrafish - genetics
Zebrafish Proteins - genetics
Zebrafish Proteins - metabolism
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0408318102