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Development ePress online publication date 24 Jan 2007
doi: 10.1242/dev.003244
Research report
Endothelial signalling by the Notch ligand Delta-like 4 restricts angiogenesis
Jonathan D. Leslie*,
Linda Ariza-McNaughton,
Adam L. Bermange,
Ryan McAdow,
Stephen L. Johnson,
and
Julian Lewis
* Author for correspondence (e-mail: jonathan.leslie{at}cancer.org.uk)
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.
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© The Company of Biologists Ltd 2007
