Development of the epicardium and its role during regeneration

The epicardium is a unicellular epithelial layer of that envelops the myocardium. It derives from the proepicardium (PE), a group of cells that arises at the inflow tract of the forming heart. PE cells attach to the myocardium and form an epithelial covering, called the epicardium. During development, epicardial derived cells (EPDCs) delaminate from the embryonic epicardium, undergo epithelial-mesenchymal transition (EMT), and differentiate into smooth muscle and vascular endothelial cells of the coronary vasculature and into cardiac interstitial fibroblasts. An additional differentiation of EPDCs into cardiomyocytes is currently under debate. The epicardium also promotes the development of the myocardium through a paracrine action. In the adult, damage to the myocardium leads to the rapid reexpression of epicardial genes such as Wilms tumour 1 encoding gene (Wt1). Also, an early response to cardiac damage is the formation of a thickened epicardial cap over the injured area. These observations suggest a role for the epicardium as a source both of signals and of progenitor cells during cardiac regeneration.

We use the zebrafish as a model system to analyze the molecular mechanisms of epicardium formation in vivo. The zebrafish heart is also a well-established model for the study of cardiac regeneration, given its capacity to regenerate cardiac tissue after injury. We have recently described the use of cryoinjury for inducing cardiac injury in zebrafish. Heart cryoinjury induces massive cell death and the formation of a fibrotic scar, resembling the outcome of myocardial infarction in mammals. Importantly, unlike mammals, the zebrafish is able to remove these massive fibrotic heart lesions and regenerate the lost tissue, indicating the existence of endogenous mechanisms that allow the degradation of fibrotic tissue and its replacement by newly-formed cells.

Our work is aimed at understanding the morphogenesis of the epicardium and its role as a source of cells and signals during development and regeneration. A second main goal of the laboratory is to elucidate the molecular mechanisms of fibrotic tissue degradation in zebrafish.