Notch signaling is required for arterial-venous differentiation during embryonic vascular development

Recent evidence indicates that acquisition of artery or vein identity durin g vascular development is governed, in part, by genetic mechanisms. The art ery-specific expression of a number of Notch signaling genes in mouse and z ebrafish suggests that this pathway may play a role in arterial-venous cell fate determination during vascular development. We show that loss of Notch signaling in zebrafish embryos leads to molecular defects in arterial-veno us differentiation, including loss of artery-specific markers and ectopic e xpression of venous markers within the dorsal aorta. Conversely, we find th at ectopic activation of Notch signaling leads to repression of venous cell fate. Finally, embryos lacking Notch function exhibit defects in blood ves sel formation similar to those associated with improper arterial-venous spe cification. Our results suggest that Notch signaling is required for the pr oper development of arterial and venous blood vessels, and that a major rol e of Notch signaling in blood vessels is to repress venous differentiation within developing arteries.