Heterogeneous pdgfrβ+ cells regulate coronary vessel development and revascularization during heart regeneration

ABSTRACT Endothelial cells emerge from the atrioventricular canal (AVC) to form nascent coronary blood vessels in the juvenile zebrafish heart. We found that pdgfrβ is first expressed in the epicardium around the AVC and later becomes localized mainly in the mural cells. pdgfrβ mutant fish display severe defects in mural cell recruitment and coronary vessel development. pdgfrβ+ mural cells are heterogeneous and those associated with coronary arteries also express cxcl12b . Mural cells positive for both pdgfrβ and cxcl12b transgenic reporters had elevated expression of smooth muscle cell genes. Interestingly, these mural cells were associated with coronary arteries even in the absence of Pdgfrβ, although smooth muscle gene expression was downregulated in these cells. We found that pdgfrβ expression dynamically changes in the epicardium derived cells, which we found to be a heterogeneous population. mdka was identified as a gene upregulated in subpopulations of pdgfrβ + cells during heart regeneration. However, pdgfrβ but not mdka mutants showed defects in heart regeneration. Our results demonstrated that pdgfrβ+ cells and Pdgfrβ signaling are essential for coronary development and heart regeneration. SUMMARY STATEMENT Heterogeneous pdgfrβ positive cells are present in developing and regenerating zebrafish hearts and are required for development of mural cells and their association with the nascent coronary vessels during zebrafish heart development and regeneration.