Abstract

In zebrafish, the spatiotemporal development of the vascular system is well described due to its stereotypical nature. However, the cellular and molecular mechanisms orchestrating post-embryonic vascular development, the maintenance of vascular homeostasis, or how coronary vessels integrate into the growing heart are less well studied. In the context of cardiac regeneration, the central cellular mechanism by which the heart regenerates a fully functional myocardium relies on the proliferation of pre-existing cardiomyocytes; the epicardium and the endocardium are also known to play key roles in the regenerative process. Remarkably, revascularisation of the injured tissue occurs within a few hours after cardiac damage, thus generating a vascular network acting as a scaffold for the regenerating myocardium. The activation of the endocardium leads to the secretion of cytokines, further supporting the proliferation of the cardiomyocytes. Although epicardium, endocardium, and myocardium interact with each other to orchestrate heart development and regeneration, in this review, we focus on recent advances in the understanding of the development of the endocardium and the coronary vasculature in zebrafish as well as their pivotal roles in the heart regeneration process.

Highlights

  • In zebrafish, the spatiotemporal development of the vascular system is well described due to its stereotypical nature

  • We first describe the key stages of endocardium and coronary vessel development and focus on how these different endothelial cell populations contribute to heart regeneration

  • It is essential to investigate the interplay between infiltrating leucocytes, the endocardium, and coronary vasculature to better understand the pro-angiogenic effects elicited by inflammation in zebrafish heart regeneration

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Summary

The Endothelium in Heart Development

In the past 25 years, the zebrafish model has facilitated a wealth of discoveries about angiogenesis and cardiac morphogenesis. The use of morpholinos to simulate the “loss of function” of genes of interest involved in angiogenic processes has been challenged since the observation of Kok and colleagues that a number of genuine loss of function genetic mutant animals failed to phenocopy vascular deformations observed in the corresponding morpholino-injected animals [14]. This caused a significant shift in how morpholinos are used in the laboratory [15] and promoted the adoption of CRISPR/Cas and similar gene editing techniques to create mutant allele-harbouring zebrafish lines. Their study prompted a more nuanced understanding of what underlying biological mechanisms can cause this discrepancy, ranging from within-pathway compensation to cellular stress response and evolutionary divergence of protein function [16,17,18,19]

Heart Development in Zebrafish
Endocardial Development and Function
Development of the Coronary Vessels Occurs Late during Zebrafish Development
The Endothelium in Heart Regeneration
Inflammation
Endothelial Cell Migration
Metabolic Modulation
Vascular Endothelial Growth Factor
Neuregulin1
Cxcl12—Cxcr4 signalling
Fibroblast Growth Factor
Platelet Derived Growth Factor
Neuropilins
Aldh1a2
The Lymphatic Vasculature in Zebrafish Heart Regeneration
Findings
Summary
Full Text
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