PUBLICATION
Inhibition of Endothelial Cell Apoptosis by Netrin-1 during Angiogenesis
- Authors
- Castets, M., Coissieux, M.M., Delloye-Bourgeois, C., Bernard, L., Delcros, J.G., Bernet, A., Laudet, V., and Mehlen, P.
- ID
- ZDB-PUB-090424-28
- Date
- 2009
- Source
- Developmental Cell 16(4): 614-620 (Journal)
- Registered Authors
- Laudet, Vincent
- Keywords
- DEVBIO
- MeSH Terms
-
- Tumor Suppressor Proteins/pharmacology*
- Mice
- Apoptosis Regulatory Proteins/metabolism
- In Vitro Techniques
- Protein Binding/drug effects
- Animals
- Neovascularization, Physiologic/drug effects*
- Humans
- Death-Associated Protein Kinases
- Enzyme Inhibitors/pharmacology
- Zebrafish/embryology
- Endothelial Cells/cytology*
- Endothelial Cells/drug effects*
- Endothelial Cells/enzymology
- Apoptosis/drug effects*
- Calcium-Calmodulin-Dependent Protein Kinases/metabolism
- Gene Silencing/drug effects
- Caspase Inhibitors
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/drug effects
- Nerve Growth Factors/pharmacology*
- Phenotype
- Rats
- Blood Vessels/abnormalities
- Blood Vessels/drug effects
- Receptors, Cell Surface/metabolism
- PubMed
- 19386270 Full text @ Dev. Cell
Citation
Castets, M., Coissieux, M.M., Delloye-Bourgeois, C., Bernard, L., Delcros, J.G., Bernet, A., Laudet, V., and Mehlen, P. (2009) Inhibition of Endothelial Cell Apoptosis by Netrin-1 during Angiogenesis. Developmental Cell. 16(4):614-620.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping