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

Abstract

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.

Endothelial Cell Dynamics in Vascular Development: Insights From Live-Imaging in Zebrafish

“…Visualize F-actin polymerization on F-actin-based structures in endothelial cells such as filopodia and endothelial cell junctions Helker et al, 2013;Phng et al, 2013;Sauteur et al, 2014;Aydogan et al, 2015;Gebala et al, 2016;Hamm et al, 2016;Sauteur et al, 2017;Sugden et al, 2017;Paatero et al, 2018;Weijts et al, 2018;Kugler et al, 2019;Savage et al, 2019 Tg(4XUAS:mClavGR2-Has.UTRN) ubs27…”

Oscillatory fluid-induced mechanobiology in heart valves with parallels to the vasculature

“…Analyses also suggests that differentiation of arterial or venous phenotype is mainly regulated by flow (6). For instance, vascular remodeling in zebrafish has shown transformation of arterial intersegmental vessels into venous phenotypes to create efficient blood circulation (101). This phenomenon demonstrates the plasticity of the vascular endothelium and that arterial and venous expressions may be reversible, depending on the flow environment (102,103).…”

Unraveling Endothelial Cell Phenotypic Regulation By Spatial Hemodynamic Flows With Microfluidics

“…Since polarization and morphology both responded to distinct SPF, we hypothesized that helical and chaotic SPF may be differentially sensed by the EC mechanosensors. We focused on NOTCH1, which is an essential regulator of EC junctional integrity, alignment and elongation, as well as of PCP and migration (45)(46)(47). Inhibition of NOTCH1 signaling has been shown to adversely alter hEC polarization to flow (45).…”