Journal
DEVELOPMENTAL CELL
Volume 16, Issue 4, Pages 614-620Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2009.02.006
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Funding
- Ligue Contre le Cancer
- Agence Nationale de la Recherche
- Institut National du Cancer
- Centre National de la Recherche Scientifique
- Centre Leon Berard
- Fondation pour la Recherche Medicale
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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.
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