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

Xiaowel 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, Anne Eichmann

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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.

Original languageEnglish
Pages (from-to)179-186
Number of pages8
JournalNature
Volume432
Issue number7014
DOIs
Publication statusPublished - Nov 11 2004
Externally publishedYes

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Lu, X., Le Noble, F., Yuan, L., Jiang, Q., De Lafarge, B., Sugiyama, D., ... Eichmann, A. (2004). The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system. Nature, 432(7014), 179-186. https://doi.org/10.1038/nature03080