Notch signalling through the ligand Delta-like 4 (Dll4) is essential for normal vascular development, but which aspect of endothelial cell behaviour does this signalling pathway control? Leslie et al. now show for the first time that, in zebrafish embryos, Dll4-Notch signalling tells endothelial cells to stop migrating and proliferating (behaviours that form new sprouts on existing vessels) once a vascular circuit has been completed (see ). The researchers report that, although blood vessel formation starts normally in embryos in which Dll4 production has been blocked with a morpholino antisense oligonucleotide, the embryos develop a network of aberrant interconnected branches unless vascular endothelial growth factor (VEGF) signalling is also blocked. Ectopic activation of Notch, by contrast, prevents endothelial sprouts forming. The researchers conclude that Notch signalling acts as an angiogenic `off' switch in endothelial cells exposed to VEGF. Thus, given the recent demonstration that Dll4 blockade decreases tumour growth in mice by promoting nonproductive angiogenesis, targeting Dll4 could provide a new way to treat cancer.
