Fig. 9

Overexpression of hand2 boosts cardiomyocyte proliferation in response to injury. (A) Schematic representation of transgenes used for cardiomyocyte ablation and myocardium-specific hand2 overexpression in Z-CAT fish. (B) Proliferation indices for ventricular cardiomyocytes; error bars indicate s.e.m. Proliferation was assessed 7days after 4-HT injection in Z-CAT fish with or without induced cardiomyocyte-specific hand2 overexpression. hand2-overexpressing fish exhibited significantly increased proliferation following ablation injury (n=9 or 10; *P<0.05). (C) Proliferation indices in injured cmlc2:CreER; β-act2:RSH fish; error bars indicate s.e.m. Proliferation was assessed at the resection plane 7days post-amputation (dpa) in animals that were injected with either vehicle or 4-HT 5days before injury. hand2-overexpressing fish exhibited significantly increased proliferation following resection injury (n=4 or 5; *P<0.005). (D,E) Representative examples of cardiomyocyte proliferation at 7dpa at the resection plane (brackets) in injured cmlc2:CreER; β-act2:RSH fish that were treated with vehicle (D) or 4-HT (E). Mef2 (green) marks cardiomyocytes and PCNA (red) marks proliferating cells; arrows in insets indicate double-positive cells.