Advances in understanding the mechanism of zebrafish heart regeneration

• Zebrafish possess enhanced capacity for heart regeneration.
• Cardiomyocytes generate cardiac muscle in natural heart regeneration models.
• Primordial, cortical, and trabecular muscles are defined in the zebrafish heart.
• Atrial myocytes can transdifferentiate into ventricular muscles during regeneration.
• Zebrafish research may provide implications for heart regeneration in humans.

The adult mammalian heart was once believed to be a post-mitotic organ without any capacity for regeneration, but recent findings have challenged this dogma. A modified view assigns the mammalian heart a measurable capacity for regeneration throughout its lifetime, with the implication that endogenous regenerative capacity can be therapeutically stimulated in the injury setting. Although extremely limited in adult mammals, the natural capacity for organ regeneration is a conserved trait in certain vertebrates. Urodele amphibians and teleosts are well-known examples of such animals that can efficiently regenerate various organs including the heart as adults. By understanding how these animals regenerate a damaged heart, one might obtain valuable insights into how regeneration can be augmented in injured human hearts. Among the regenerative vertebrate models, the teleost zebrafish, Danio rerio, is arguably the best characterized with respect to cardiac regenerative responses. Knowledge is still limited, but a decade of research in this model has led to results that may help to understand how cardiac regeneration is naturally stimulated and maintained. This review surveys recent advances in the field and discusses current understanding of the endogenous mechanisms of cardiac regeneration in zebrafish.