Abstract
Insight into the role of the epicardium in cardiac development and regeneration has significantly improved over the past ten years. This is mainly due to the increasing availability of new mouse models for the study of the epicardial lineage. Here we focus on the growing understanding of the significance of the epicardium and epicardially-derived cells in the formation of the atrioventricular (AV) junction. First, through the process of epicardial epithelial-to-mesenchymal transformation (epiEMT), the subepicardial AV mesenchyme is formed. Subsequently, the AV-epicardium and epicardially-derived cells (EPDCs) form the annulus fibrosus, a structure important for the electrical separation of atrial and ventricular myocardium. Finally, the AV-EPDCs preferentially migrate into the parietal AV valve leaflets, largely replacing the endocardially-derived cell population. In this review, we provide an overview of what is currently known about the regulation of the events involved in this process.
Highlights
Academic Medical Center, Heart Failure Research Center, Department of Anatomy, Embryology and Physiology, Meibergdreef 15, 1105AZ, Amsterdam, The Netherlands; Tel.: +1-843-792-8183; Fax: +1-843-792-0664
The heart develops from two populations of cardiogenic anterior lateral plate mesodermal cells, known as the First Heart Fields (FHFs), which join at the ventral embryonic midline to form the primary heart tube
This tube is comprised of three layers; an outer layer of primary myocardium, a middle layer of extracellular matrix-rich cardiac jelly, and an inner layer of endocardial cells which lines the lumen of the heart [2]
Summary
The AV valves are crucial structures in the developed 4-chambered heart. When properly formed, they prevent retrograde flow of blood from ventricles to atria during ventricular systole. Septum and the dorsal mesenchymal protrusion (DMP) to form the AV mesenchymal complex [17] This complex contributes to the partition of the atrial and ventricular cavities and plays a role in the formation of the AV valve leaflets that are associated with the AV septal structures, i.e., the septal leaflet of the tricuspid valve and the aortic (or anterior) leaflet of the mitral valve [17,18]. In addition to the major cushions, two smaller AV cushions form at the lateral AV myocardial junctions These “lateral AV cushions” (right and left) develop around the time the superior and inferior cushions are fusing and, like the major cushions, become populated with mesenchymal cells as a result of endoEMT. Throughout this review, the AV valve leaflets that derive from the right and left lateral cushions will be referred to as the parietal leaflets
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