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First published online 24 January 2007
doi: 10.1242/dev.003244
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Research Report |
1 Vertebrate Development Laboratory, Cancer Research UK London Research
Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
2 Department of Genetics, Box 8232, Washington University Medical School, 4566
Scott Avenue, St Louis, MO 63110, USA.
* Author for correspondence (e-mail: jonathan.leslie{at}cancer.org.uk)
Accepted 31 December 2007
SUMMARY
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.
Key words: Notch, Delta-like 4, Angiogenesis, Endothelial, Motility, Zebrafish
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