Fig. 8

Fig. 8. Quantitative model of zebrafish heart regeneration via proliferation of lineage-restricted cardiomyocytes. (A) Model of cardiomyocyte fate during zebrafish heart regeneration. Cardiomyocytes dedifferentiate, which entails loss of sarcomeres, alterations in calcium transients and gain of embryonic markers, but not attainment of multipotency. (B) Model of the time-courses of cardiomyocyte regeneration and wound resorption. Restoration of pre-injury cardiomyocyte numbers (green) in response to cryoinjury, which kills about 30% of the cardiomyocytes, is achieved within 30 days. The morphological septation between trabecular layer (pink) and cortical layer (brown) is restored. Despite completed cardiomyocyte regeneration, the majority of hearts still contain scars at 30 and 90 dpi. Regenerated cardiomyocytes in scar-free ventricles or at the internal wound border zone retain normal density and fully re-differentiate (blue). Some of the regenerated cardiomyocytes (3–15%) located externally to remaining internalized scars are smaller and only partially re-differentiated (yellow). In scarred hearts, fibrosis persists beyond 30 dpi.