The embryonic epicardium originates from the proepicardium, an extracardiac primordium
constituted by a cluster of mesothelial cells. In early embryos, the embryonic epicardium is characterized
by a squamous cell epithelium resting on the myocardium surface. Subsequently, it invades the
subepicardial space and thereafter the embryonicmyocardiumbymeans of an epithelial–mesenchymal
transition.Within the myocardium, epicardial-derived cells present multilineage potential, later differentiating
into smoothmuscle cells and contributing both to coronary vasculature and cardiac fibroblasts
in themature heart. Over the last decades, we have progressively increased our understanding of those
cellular and molecular mechanisms driving proepicardial/embryonic epicardium formation. This
study provides a state-of-the-art review of the transcriptional and emerging post-transcriptional
mechanisms involved in the formation and differentiation of the embryonic epicardium.
