Temporal inhibition of Trpv4, Notch and NO signaling differentially affects ventricle regeneration. A–C Quantification of the heart recovery rate at 96 hpt in ablated groups treated with HC-067047 (TRPV4 antagonist), DAPT (Notch signaling inhibitor) or L-NMMA (NO synthase inhibitor) at different stages. The numbers of larvae analyzed for each condition are indicated. Binomial test; ns, not significant; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. D–H′ Immunostaining of anti-phospho-histone H3 (pH3, green) and anti-myosin heavy chain (MF-20, red) in the hearts of control and ablated groups at 48 or 72 hpt with DMSO, HC-067047, DAPT or L-NMMA treatment for 0–24 or 48–72 hpt. I, J Quantification of pH3+ cardiomyocyte numbers in control and ablated hearts treated with DMSO, HC-067047, DAPT or L-NMMA for 0–24 or 48–72 hpt. N = 11 for each group. Mean + s.e.m. ANOVA analysis; ns, not significant; *P < 0.05, ****P < 0.0001. K–O′ Confocal images of Tg(vmhc:mCherry-NTR; amhc:CreERT2; β-act2:RSG) control and ablated hearts at 72 hpt with DMSO, HC-067047, DAPT or L-NMMA treatment for 0–24 or 48–72 hpt. P, Q Quantification of the percentages of GFP-positive area in control or ablated ventricles with DMSO, HC-067047, DAPT or L-NMMA treatment for 0–24 or 48–72 hpt. N = 10 for each group. Mean + s.e.m. ANOVA analysis; *P < 0.05, ****P < 0.0001. Scale bars, 50 μm. Dashed lines outline the hearts. hpt hours post treatment, HC HC-067047
|
