Figure 1.

Differential gene expression affects regenerative ability. (A) Fstl1 expression in the mouse heart is altered upon injury. In uninjured hearts, the epicardium produces Fstl1, which has the potential to promote cardiomyocyte (CM) proliferation. However, in injured hearts, Fstl1 is mainly produced by the myocardium rather than the epicardium. Fstl1 derived from the myocardium appears to be unable to promote CM proliferation due to glycosylation. (B) The level of Erbb2, a receptor of Nrg1, declines after birth, resulting in poor regenerative capacity in the mouse heart. (C) In zebrafish, Erbb2 expression is maintained throughout life, and a sustained Erbb2 level contributes to retaining cardiac regenerative capacity in the adult stage. (D) The expression level of the miRNA-15 family and miRNA-128 increases after birth in mice to inhibit heart regeneration. However, it is unclear whether expression of these miRNA is maintained upon injury. (E) The expression level of miRNA-101a is dynamic during heart regeneration in adult zebrafish. Depletion of miRNA-101a in the early regenerative stage promotes CM proliferation, while the presence of miRNA-101a in the late regenerative stage contributes to scar tissue removal. The ability to precisely modulate miRNA expression during heart regeneration enables zebrafish to retain remarkable regenerative capacity. In (B,D): E/F, embryonic/fetal period; B, birth; P, postnatal period.