2010 March 25 | 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
A study published in Nature (2010) reveals that gata4+ cardiomyocytes play a key role in zebrafish heart regeneration. Researchers used genetic fate-mapping techniques to show that these cells become activated after resection of the ventricular apex and contribute significantly to cardiac muscle regeneration. They found that gata4 expression is triggered in cardiomyocytes within the subepicardial ventricular layer within a week of injury, and these cells proliferate and contribute to the regeneration of the heart muscle. Using transgenic reporter strains, they observed that gata4:EGFP fluorescence was induced in a high percentage of cells in the outer compact layer of ventricular myocardium after injury. These cells were found to be positive for myocyte markers and negative for epicardial markers. BrdU labeling studies showed that many gata4:EGFP+ cells at the wound edges had recently undergone DNA synthesis. By 30 days post-injury, a substantial area of the regenerated ventricular wall remained labeled by gata4:EGFP fluorescence. These findings indicate that electrically coupled cardiac muscle regenerates after resection injury primarily through activation and expansion of cardiomyocyte populations. The study also shows that existing cardiomyocytes contribute significantly to regeneration, as evidenced by the labeling of a majority of cardiac muscle in the regenerate. The results suggest that the zebrafish heart's regenerative response is effective in restoring function and that the presence of a scar does not prevent regeneration. The study highlights the importance of gata4 in heart regeneration and provides insights into the cellular and molecular mechanisms underlying this process. The findings have implications for promoting regeneration of the injured human heart. The study also discusses the use of genetic tools in zebrafish to enable precise experimental manipulation of gene expression or function in attempts to modify the injury environment or regenerative response. The study provides a detailed methodology for the construction of transgenic animals and the quantification of EGFP fluorescence in cmlc2:CreER;β-act2:RSG animals. The study also includes optical mapping data showing that electrical coupling of new apical cardiomyocytes begins to occur by about 2 weeks post-injury, with full coupling in the restored wall by 30 days. The study also discusses the role of gata4 in heart regeneration and the potential for using zebrafish as a model for understanding human heart regeneration. The study concludes that the zebrafish heart's regenerative response is effective in restoring function and that the presence of a scar does not prevent regeneration. The study provides a detailed methodology for the construction of transgenic animals and the quantification of EGFP fluorescence in cmlc2:CreER;β-act2:RSG animals. The study also includes optical mapping data showing that electrical coupling of new apical cardiomyocytes begins to occur by about 2 weeks post-injury, with full coupling in theA study published in Nature (2010) reveals that gata4+ cardiomyocytes play a key role in zebrafish heart regeneration. Researchers used genetic fate-mapping techniques to show that these cells become activated after resection of the ventricular apex and contribute significantly to cardiac muscle regeneration. They found that gata4 expression is triggered in cardiomyocytes within the subepicardial ventricular layer within a week of injury, and these cells proliferate and contribute to the regeneration of the heart muscle. Using transgenic reporter strains, they observed that gata4:EGFP fluorescence was induced in a high percentage of cells in the outer compact layer of ventricular myocardium after injury. These cells were found to be positive for myocyte markers and negative for epicardial markers. BrdU labeling studies showed that many gata4:EGFP+ cells at the wound edges had recently undergone DNA synthesis. By 30 days post-injury, a substantial area of the regenerated ventricular wall remained labeled by gata4:EGFP fluorescence. These findings indicate that electrically coupled cardiac muscle regenerates after resection injury primarily through activation and expansion of cardiomyocyte populations. The study also shows that existing cardiomyocytes contribute significantly to regeneration, as evidenced by the labeling of a majority of cardiac muscle in the regenerate. The results suggest that the zebrafish heart's regenerative response is effective in restoring function and that the presence of a scar does not prevent regeneration. The study highlights the importance of gata4 in heart regeneration and provides insights into the cellular and molecular mechanisms underlying this process. The findings have implications for promoting regeneration of the injured human heart. The study also discusses the use of genetic tools in zebrafish to enable precise experimental manipulation of gene expression or function in attempts to modify the injury environment or regenerative response. The study provides a detailed methodology for the construction of transgenic animals and the quantification of EGFP fluorescence in cmlc2:CreER;β-act2:RSG animals. The study also includes optical mapping data showing that electrical coupling of new apical cardiomyocytes begins to occur by about 2 weeks post-injury, with full coupling in the restored wall by 30 days. The study also discusses the role of gata4 in heart regeneration and the potential for using zebrafish as a model for understanding human heart regeneration. The study concludes that the zebrafish heart's regenerative response is effective in restoring function and that the presence of a scar does not prevent regeneration. The study provides a detailed methodology for the construction of transgenic animals and the quantification of EGFP fluorescence in cmlc2:CreER;β-act2:RSG animals. The study also includes optical mapping data showing that electrical coupling of new apical cardiomyocytes begins to occur by about 2 weeks post-injury, with full coupling in the