Figure 4

Dynamics of zebrafish heart regeneration. Representations of a region of the zebrafish heart in the absence of injury (A) or at different stages after cryoinjury (B−F). (B) Ventricular cryoinjury induces local tissue necrosis (gray) and apoptosis in all cell types around the injured region. Tissue death triggers the recruitment of inflammatory cells and endocardial activation. (C) During the first days after injury, epicardial and endocardial cells proliferate actively and cover the injured area, establishing a “regenerative scaffold.” Epicardial cells also undergo epithelial to mesenchymal transitions and invade the underlying myocardium. Myofibroblasts appear in the injury zone and there is an accumulation of extracellular matrix. (D−E) Cardiomyocytes located in the wound edge proliferate and repopulate the injured area. As the myocardium regenerates, the fibrotic tissue progressively disappears. (F) In advanced stages of regeneration, the zebrafish myocardium appears completely restored. Compared to uninjured controls or to the contralateral wall, the regenerated wall shows a significant expansion of the cortical myocardium. dpi, days post‐injury; ECM, extracellular matrix; EP, epicardium; PVC, perivascular cell