Endothelial signalling by the Notch ligand Delta-like 4 restricts angiogenesis.
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.
Leslie
Jonathan D
JD
Vertebrate Development Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Ariza-McNaughton
Linda
L
Bermange
Adam L
AL
McAdow
Ryan
R
Johnson
Stephen L
SL
Lewis
Julian
J
D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000196:embryology / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000502:physiology*; D018919:Neovascularization, Physiologic; D051880:Receptors, Notch / Q000502:physiology*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology; D015027:Zebrafish / Q000196:embryology / Q000502:physiology*; D029961:Zebrafish Proteins / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; D042461:Vascular Endothelial Growth Factor A; D029961:Zebrafish Proteins; C064045:delta protein