Dedifferentiation, Transdifferentiation, and Proliferation: Mechanisms Underlying Cardiac Muscle Regeneration in Zebrafish

The adult mammalian heart is increasingly recognized as a regenerative organ with a measurable capacity to replenish cardiomyocytes throughout its lifetime, illuminating the possibility of stimulating endogenous regenerative capacity to treat heart diseases. Unlike mammals, certain vertebrates possess robust capacity for regenerating a damaged heart, providing a model to understand how regeneration could be augmented in injured human hearts. Facilitated by its rich history in the study of heart development, the teleost zebrafish Danio rerio has been established as a robust model to investigate the underlying mechanism of cardiac regeneration. This review discusses the current understanding of the endogenous mechanisms behind cardiac regeneration in zebrafish, with a particular focus on cardiomyocyte dedifferentiation, transdifferentiation, and proliferation.