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

Author

Listed:
  • 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
    South China Agricultural University)

  • 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
    Genentech Inc.)

  • Anne Eichmann

    (INSERM U 36, Collège de France)

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.

Suggested Citation

  • 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 Car, 2004. "The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system," Nature, Nature, vol. 432(7014), pages 179-186, November.
    • Handle: RePEc:nat:nature:v:432:y:2004:i:7014:d:10.1038_nature03080
    DOI: 10.1038/nature03080
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    Cited by:

    1. Kevin Boyé & Luiz Henrique Geraldo & Jessica Furtado & Laurence Pibouin-Fragner & Mathilde Poulet & Doyeun Kim & Bryce Nelson & Yunling Xu & Laurent Jacob & Nawal Maissa & Dritan Agalliu & Lena Claess, 2022. "Endothelial Unc5B controls blood-brain barrier integrity," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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