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

Bart Weijts,Semion K Saikin,Edgar Gutierrez,Alex Groisman,David Traver,Eugene Tkachenko,Ararat J Ablooglu

doi:10.1038/s41467-018-07732-7

Bart Weijts, Semion K Saikin + Show 5 more

Open Access

https://doi.org/10.1038/s41467-018-07732-7

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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.

Highlights

Arteries and veins are formed independently by different types of endothelial cells (ECs)
We studied vascular remodeling in embryonic zebrafish and found that venous identity of intersegmental vessels (ISVs) is established by displacement of arterial ECs with venous ECs migrating into ISVs from the posterior cardinal vein (PCV) without trans-differentiation of ECs
The proportion of venous ISVs at 60 hpf increased to significantly greater than 50% (Fig. 1b, c; Supplementary Fig. 1a, b). These venous ISVs were lined with venous ECs only in ventral parts, whereas their dorsal parts remained lined with arterial ECs (Fig. 1b)

Summary

Introduction

Arteries and veins are formed independently by different types of endothelial cells (ECs). 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. Vascular remodeling transforms arterial intersegmental vessels (ISVs) into a functional network of arteries and veins. All ISVs are arterial with no blood flow, and the remodeling transforms them into a balanced functional network with nearly equal numbers of arteries and veins. We studied vascular remodeling in embryonic zebrafish and found that venous identity of ISVs is established by displacement of arterial ECs with venous ECs migrating into ISVs from the PCV without trans-differentiation of ECs. We found that once an ISV is fate-determined to transform into a vein, the pattern of newly established blood flow leads to a strong bias for the two adjacent ISVs to remain arteries

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