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The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system

Item Type:Article
Title:The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system
Creators Name:Lu, X. and Le Noble, F. and Yuan, L. and Jiang, Q. and De Lafarge, B. and Sugiyama, D. and Breant, C. and Claes, F. and De Smet, F. and Thomas, J.L. and Autiero, M. and Carmeliet, P. and Tessier-Lavigne, M. and Eichmann, A.
Abstract:Blood vessels and nerves are complex, branched structures that share a high degree of anatomical similarity. Guidance of vessels and nerves has to be exquisitely regulated to ensure proper wiring of both systems. Several regulators of axon guidance have been identified and some of these are also expressed in endothelial cells; however, the extent to which their guidance functions are conserved in the vascular system is still incompletely understood. We show here that the repulsive netrin receptor UNC5B is expressed by endothelial tip cells of the vascular system. Disruption of the Unc5b gene in mice, or of Unc5b or netrin-1a in zebrafish, leads to aberrant extension of endothelial tip cell filopodia, excessive vessel branching and abnormal navigation. Netrin-1 causes endothelial filopodial retraction, but only when UNC5B is present. Thus, UNC5B functions as a repulsive netrin receptor in endothelial cells controlling morphogenesis of the vascular system.
Keywords:Blood Vessels, Cell Movement, Cell Size, Endothelial Cells, Vascular Endothelium, Molecular Sequence Data, Morphogenesis, Mutation, Nerve Growth Factors, Pseudopodia, Messenger RNA, Cell Surface Receptors, Tumor Suppressor Proteins, Animals, Mice, Zebrafish
Source:Nature
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Volume:432
Number:7014
Page Range:179-186
Date:11 November 2004
Official Publication:https://doi.org/10.1038/nature03080
PubMed:View item in PubMed

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