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

Xiaowei Lu, Ferdinand le Noble, Li Yuan, Quingjan Jiang, Benjamin de Lafarge, Daisuke Sugiyama, Christiane Bréant, Filip Claes, Frederik De Smet, Jean-Léon Thomas, Monica Autiero, Peter Carmeliet, Marc Tessier-Lavigne () and Anne Eichmann ()
Additional contact information
Xiaowei Lu: Howard Hughes Medical Institute, Stanford University
Ferdinand le Noble: INSERM U 36, Collège de France
Li Yuan: INSERM U 36, Collège de France
Quingjan Jiang: INSERM U 36, Collège de France
Benjamin de Lafarge: INSERM U 36, Collège de France
Daisuke Sugiyama: Université Pierre et Marie Curie
Christiane Bréant: INSERM U 36, Collège de France
Filip Claes: University of Leuven
Frederik De Smet: University of Leuven
Jean-Léon Thomas: Hôpital de la Salpêtrière, Université Pierre et Marie Curie
Monica Autiero: University of Leuven
Peter Carmeliet: University of Leuven
Marc Tessier-Lavigne: Howard Hughes Medical Institute, Stanford University
Anne Eichmann: INSERM U 36, Collège de France

Nature, 2004, vol. 432, issue 7014, 179-186

Abstract: 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.

Date: 2004
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DOI: 10.1038/nature03080

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