Transciptional effects of coronary vessel loss on epicaridal cells in juvenile zebrafish

ABSTRACT: During cardiac development, the myocardium expands in response to physiological demands to achieve proper cardiac morphology and functional contractility, while simultaneously integrating with the developing coronary vasculature. However, the mechanisms governing this ordered expansion and the role of coronary vasculature formation in this process remain poorly understood. Here, we found that regional hypoxia drives local tissue thickening, which in turn exacerbates a hypoxic microenvironment. We demonstrate that epicardial hypoxia serves as a central regulatory mechanism, coordinating both coronary angiogenesis and myocardial expansion during juvenile zebrafish heart development. This mechanism activates discrete spatial patterns of epicardial gene expression, including for vegfaa, loxl2a, and col12a1b. Through live and fixed imaging, we find that cardiomyocytes and endothelial cells exhibit coordinated migration patterns through third-party epicardial signals. We further demonstrate that epicardial subpopulations are required for both coronary development and myocardial expansion. Using cxcr4aum20 mutants lacking functional coronary vessels, we show that coronary vessels function as a negative feedback mechanism to epicardial hypoxia, while positively responding to the same hypoxic cues that drive myocardial expansion. Importantly, disruption of this negative feedback on epicardial hypoxia also leads to increased myocardial stiffness through dysregulated extracellular matrix crosslinking. Thus, we provide mechanistic insights into pathological conditions characterized by myocardial stiffness such as cardiomyopathies. These findings establish the role of regional epicardial hypoxia within a fundamental regulatory network that drives appropriate regional tissue growth with integrated vascular supply during cardiac morphogenesis.

ORGANISM(S): Danio rerio

PROVIDER: GSE313651 | GEO | 2026/04/30

REPOSITORIES: GEO