The study investigates the source of newly formed cardiomyocytes during zebrafish heart regeneration, a process that allows the fish to fully regenerate its heart after amputation of up to 20% of the ventricle. Using a genetic strategy based on the Cre/lox system, the researchers found that regenerated heart muscle cells are derived from the proliferation of differentiated cardiomyocytes. These cardiomyocytes undergo limited dedifferentiation, characterized by the disassembly of their sarcomeric structure, detachment from each other, and expression of regulators of cell cycle progression. Specifically, polo-like kinase 1 (plk1) was identified as an essential component of cardiomyocyte proliferation during heart regeneration. The findings provide direct evidence that stem/progenitor cells are not significantly involved in this process, and suggest that the regenerative response is primarily driven by pre-existing cardiomyocytes.The study investigates the source of newly formed cardiomyocytes during zebrafish heart regeneration, a process that allows the fish to fully regenerate its heart after amputation of up to 20% of the ventricle. Using a genetic strategy based on the Cre/lox system, the researchers found that regenerated heart muscle cells are derived from the proliferation of differentiated cardiomyocytes. These cardiomyocytes undergo limited dedifferentiation, characterized by the disassembly of their sarcomeric structure, detachment from each other, and expression of regulators of cell cycle progression. Specifically, polo-like kinase 1 (plk1) was identified as an essential component of cardiomyocyte proliferation during heart regeneration. The findings provide direct evidence that stem/progenitor cells are not significantly involved in this process, and suggest that the regenerative response is primarily driven by pre-existing cardiomyocytes.