Development of the endocardium

Abstract

The endocardium, the endothelial lining of the heart, plays complex and critical roles in heart development, particularly in the formation of the cardiac valves and septa, the division of the truncus arteriosus into the aortic and pulmonary trunks, the development of Purkinje fibers that form the cardiac conduction system, and the formation of trabecular myocardium. Current data suggest that the endocardium is a regionally specialized endothelium that arises through a process of de novo vasculogenesis from a distinct population of mesodermal cardiogenic precursors in the cardiac crescent. In this article, we review recent developments in the understanding of the embryonic origins of the endocardium. Specifically, we summarize vasculogenesis and specification of endothelial cells from mesodermal precursors, and we review the transcriptional pathways involved in these processes. We discuss the lineage relationships between the endocardium and other endothelial populations and between the endocardium and the myocardium. Finally, we explore unresolved questions about the lineage relationships between the endocardium and the myocardium. One of the central questions involves the timing with which mesodermal cells, which arise in the primitive streak and migrate to the cardiac crescent, become committed to an endocardial fate. Two competing conceptual models of endocardial specification have been proposed. In the first, mesodermal precursor cells in the cardiac crescent are prespecified to become either endocardial or myocardial cells, while in the second, fate plasticity is retained by bipotential cardiogenic cells in the cardiac crescent. We propose a third model that reconciles these two views and suggest future experiments that might resolve this question.

Fig. 1

A prespecification model for endocardial cells. Data obtained primarily from avian and fish models suggest that mesodermal cells are prespecified in the primitive streak before migration to the cardiac crescent to adopt either an endocardial or a myocardial fate. Endocardial precursors then receive inductive cues from the underlying endoderm to differentiate into cells with an endothelial phenotype

Fig. 2

A model for multipotent progenitor cells in the cardiac crescent. Data acquired primarily from mouse fate-mapping studies and ex vivo approaches using cells from mouse embryos suggest that there are multipotential progenitors in the cardiac crescent that can then be specified to adopt endocardial, myocardial, or vascular smooth muscle cell fates