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The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system
Authors:Lu Xiaowei  Le Noble Ferdinand  Yuan Li  Jiang Quingjan  De Lafarge Benjamin  Sugiyama Daisuke  Bréant Christiane  Claes Filip  De Smet Frederik  Thomas Jean-Léon  Autiero Monica  Carmeliet Peter  Tessier-Lavigne Marc  Eichmann Anne
Institution:Department of Biological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
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.
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