ZFIN ID: ZDB-PUB-090424-28
Inhibition of Endothelial Cell Apoptosis by Netrin-1 during Angiogenesis
Castets, M., Coissieux, M.M., Delloye-Bourgeois, C., Bernard, L., Delcros, J.G., Bernet, A., Laudet, V., and Mehlen, P.
Date: 2009
Source: Developmental Cell   16(4): 614-620 (Journal)
Registered Authors: Laudet, Vincent
Keywords: DEVBIO
MeSH Terms:
  • Animals
  • Apoptosis/drug effects*
  • Apoptosis Regulatory Proteins/metabolism
  • Blood Vessels/abnormalities
  • Blood Vessels/drug effects
  • Calcium-Calmodulin-Dependent Protein Kinases/metabolism
  • Caspase Inhibitors
  • Death-Associated Protein Kinases
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/drug effects
  • Endothelial Cells/cytology*
  • Endothelial Cells/drug effects*
  • Endothelial Cells/enzymology
  • Enzyme Inhibitors/pharmacology
  • Gene Silencing/drug effects
  • Humans
  • In Vitro Techniques
  • Mice
  • Neovascularization, Physiologic/drug effects*
  • Nerve Growth Factors/pharmacology*
  • Phenotype
  • Protein Binding/drug effects
  • Rats
  • Receptors, Cell Surface/metabolism
  • Tumor Suppressor Proteins/pharmacology*
  • Zebrafish/embryology
PubMed: 19386270 Full text @ Dev. Cell
Netrin-1 was recently proposed to play an important role in embryonic and pathological angiogenesis. However, data reported led to the apparently contradictory conclusions that netrin-1 is either a pro- or an antiangiogenic factor. Here, we reconcile these opposing observations by demonstrating that netrin-1 acts as a survival factor for endothelial cells, blocking the proapoptotic effect of the dependence receptor UNC5B and its downstream death signaling effector, the serine/threonine kinase DAPK. The netrin-1 effect on blood vessel development is mimicked by caspase inhibitors in ex vivo assays, and the inhibition of caspase activity, the silencing of the UNC5B receptor, and the silencing of DAPK are each sufficient to rescue the vascular sprouting defects induced by netrin-1 silencing in zebrafish. Thus, the proapoptotic effect of unbound UNC5B and the survival effect of netrin-1 on endothelial cells finely tune the angiogenic process.