ZFIN ID: ZDB-PUB-041029-10
The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system
Lu, X., le Noble, F., Yuan, L., Jiang, Q., de Lafarge, B., Sugiyama, D., Bréant, C., Claes, F., De Smet, F., Thomas, J.L., Autiero, M., Carmeliet, P., Tessier-Lavigne, M., and Eichmann, A.
Date: 2004
Source: Nature   432(7014): 179-186 (Journal)
Registered Authors: Tessier-Lavigne, Marc
Keywords: none
MeSH Terms:
  • Animals
  • Blood Vessels/abnormalities
  • Blood Vessels/cytology
  • Blood Vessels/embryology*
  • Blood Vessels/metabolism*
  • Cell Movement/drug effects
  • Cell Size/drug effects
  • Endothelial Cells/cytology
  • Endothelial Cells/drug effects
  • Endothelial Cells/metabolism
  • Endothelium, Vascular/cytology
  • Endothelium, Vascular/drug effects
  • Endothelium, Vascular/metabolism
  • Mice
  • Molecular Sequence Data
  • Morphogenesis*
  • Mutation/genetics
  • Nerve Growth Factors/genetics
  • Nerve Growth Factors/metabolism
  • Nerve Growth Factors/pharmacology
  • Pseudopodia/drug effects
  • Pseudopodia/metabolism
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Receptors, Cell Surface/genetics
  • Receptors, Cell Surface/metabolism*
  • Tumor Suppressor Proteins
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
PubMed: 15510105 Full text @ Nature
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.