Endothelial signalling by the Notch ligand Delta-like 4 restricts angiogenesis
Open Access
- 1 March 2007
- journal article
- Published by The Company of Biologists in Development
- Vol. 134 (5) , 839-844
- https://doi.org/10.1242/dev.003244
Abstract
Notch signalling by the ligand Delta-like 4 (Dll4) is essential for normal vascular remodelling, yet the precise way in which the pathway influences the behaviour of endothelial cells remains a mystery. Using the embryonic zebrafish, we show that, when Dll4-Notch signalling is defective, endothelial cells continue to migrate and proliferate when they should normally stop these processes. Artificial overactivation of the Notch pathway has opposite consequences. When vascular endothelial growth factor (Vegf) signalling and Dll4-Notch signalling are both blocked, the endothelial cells remain quiescent. Thus, Dll4-Notch signalling acts as an angiogenic `off' switch by making endothelial cells unresponsive to Vegf.Keywords
This publication has 40 references indexed in Scilit:
- Distinct genetic interactions between multiple Vegf receptors are required for development of different blood vessel types in zebrafishProceedings of the National Academy of Sciences, 2006
- Inhibition of endothelial cell proliferation by Notch1 signaling is mediated by repressing MAPK and PI3K/Akt pathways and requires MAML1The FASEB Journal, 2006
- Notch1b and neuregulin are required for specification of central cardiac conduction tissueDevelopment, 2006
- Up-regulation of the Notch ligand Delta-like 4 inhibits VEGF-induced endothelial cell functionBlood, 2006
- Endothelial cells and VEGF in vascular developmentNature, 2005
- Common mechanisms of nerve and blood vessel wiringNature, 2005
- Crosstalk between tumor and endothelial cells promotes tumor angiogenesis by MAPK activation of Notch signalingCancer Cell, 2005
- Cell‐autonomous notch signaling regulates endothelial cell branching and proliferation during vascular tubulogenesisThe FASEB Journal, 2005
- Delta4, an endothelial specific Notch ligand expressed at sites of physiological and tumor angiogenesisDifferentiation, 2001
- Isolation and Characterization of the Notch Ligand Delta4Experimental Cell Research, 2000