Avian embryonic coronary arterio-venous pattering involves the contribution of different endothelial and endocardial cell populations

Abstract

Background: Coronary vasculature irrigates the myocardium and is crucial to late embryonic and adult heart function. Despite the developmental significance and clinical relevance of these blood vessels, the embryonic origin and the cellular and molec- ular mechanisms that regulate coronary arterio-venous patterning are not known in detail. In this study, we have used the avian embryo to dissect the ontogenetic origin and morphogenesis of coronary vasculature. Results: We show that sinus venosus endocardial sprouts and proepicardial angioblasts pioneer coronary vascular formation, invading the developing heart simultaneously. We also report that avian ventricular endocardium has the potential to contribute to coronary vessels, and describe the incorporation of cardiac distal outflow tract endothelial cells to the peritruncal endothelial plexus to partici- pate in coronary vascular formation. Finally, our findings indicate that large sinus venosus-independent sections of the form- ing coronary vasculature develop without connection to the systemic circulation and that coronary arterio-venous shunts form a few hours before peritruncal arterial endothelium connects to the aortic root. Conclusions: Embryonic coronary vascu- lature is a developmental mosaic, formed by the integration of vascular cells from, at least, four different embryological ori- gins, which assemble in a coordinated manner to complete coronary vascular development.