Cardiac Regeneration in Zebrafish

Heart failure caused by cardiomyocyte loss after ischemic tissue damage is a leading cause of death worldwide, since adult mammals cannot regenerate heart injuries. While some new cardiomyocytes are produced in adult mammals during normal ageing and after infarction, this occurs at insufficient rates for effective cardiac regeneration. Zebrafish, on the contrary, are able to regenerate multiple organs including the heart. Injuries induce complex cellular and molecular responses in endocardium, epicardium and myocardium, which robustly regenerate in a coordinated manner, resulting in full morphological and functional recovery. In particular, differentiated cardiomyocytes re-enter the cell cycle and proliferate to regenerate the myocardium. Thus, the zebrafish has emerged as an important model to study mechanisms of naturally occurring cardiac regeneration. Here, we describe zebrafish heart injury techniques and review current data on mammalian cardiomyocyte turnover and production in response to injury as well as our current knowledge of the cellular and molecular mechanisms of zebrafish heart regeneration.