Blood flow-induced Notch activation and endothelial migration enable vascular remodeling in zebrafish embryos

Arteries and veins are formed independently by different types of endothelial cells (ECs). In vascular remodeling, arteries and veins become connected and some arteries become veins. It is unclear how ECs in transforming vessels change their type and how fates of individual vessels are determined. In embryonic zebrafish trunk, vascular remodeling transforms arterial intersegmental vessels (ISVs) into a functional network of arteries and veins. Here we find that, once an ISV is connected to venous circulation, venous blood flow promotes upstream migration of ECs that results in displacement of arterial ECs by venous ECs, completing the transformation of this ISV into a vein without trans-differentiation of ECs. Arterial blood flow initiated in two neighboring ISVs prevents their transformation into veins by activating Notch signaling in ECs. Together, different responses of ECs to arterial and venous blood flow lead to formation of a balanced network with equal numbers of arteries and veins.