Primary contribution to zebrafish heart regeneration by gata4-cardiomyocytes

Primary contribution to zebrafish heart regeneration by gata4-cardiomyocytes

2010 March 25; 464(7288): 601–605. doi:10.1038/nature08804 | Kazu Kikuchi, Jennifer E. Holdway, Andreas A. Werdich, Ryan M. Anderson, Yi Fang, Gregory F. Egnaczyk, Todd Evans, Calum A. MacRae, Didier Y. R. Stainier, and Kenneth D. Poss
This study investigates the cellular origins of zebrafish heart regeneration after ventricular apex resection. Using genetic fate-mapping approaches, the authors identified a population of cardiomyocytes that become activated and contribute significantly to the regeneration process. Specifically, they found that cardiomyocytes within the subepicardial ventricular layer trigger the expression of the embryonic cardiogenesis gene *gata4* within a week of injury, which localizes to proliferating cardiomyocytes surrounding and within the injury site. Through lineage-tracing experiments, they demonstrated that cells expressing *gata4* or the contractile gene *cmef2* before injury labeled a majority of the cardiac muscle in the regenerate. Optical voltage mapping revealed that electrical conduction between existing and regenerated cardiomyocytes is re-established between 2 and 4 weeks post-injury. Additionally, the authors showed that restoring Fgf signaling in scarred hearts can enhance regeneration without removing scar tissue. These findings highlight the importance of *gata4*-expressing cardiomyocytes in zebrafish heart regeneration and suggest potential implications for promoting human heart regeneration.This study investigates the cellular origins of zebrafish heart regeneration after ventricular apex resection. Using genetic fate-mapping approaches, the authors identified a population of cardiomyocytes that become activated and contribute significantly to the regeneration process. Specifically, they found that cardiomyocytes within the subepicardial ventricular layer trigger the expression of the embryonic cardiogenesis gene *gata4* within a week of injury, which localizes to proliferating cardiomyocytes surrounding and within the injury site. Through lineage-tracing experiments, they demonstrated that cells expressing *gata4* or the contractile gene *cmef2* before injury labeled a majority of the cardiac muscle in the regenerate. Optical voltage mapping revealed that electrical conduction between existing and regenerated cardiomyocytes is re-established between 2 and 4 weeks post-injury. Additionally, the authors showed that restoring Fgf signaling in scarred hearts can enhance regeneration without removing scar tissue. These findings highlight the importance of *gata4*-expressing cardiomyocytes in zebrafish heart regeneration and suggest potential implications for promoting human heart regeneration.
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