Fig. 6.

A preliminary model indicating requirement of foxm1 and cenpf expression in border zone cardiomyocyte cell cycle progression and mitosis. In post-injury hearts, a subpopulation of border zone cardiomyocytes express foxm1. Foxm1 transcriptionally activates expression of cell cycle genes such as cenpf, g2e3 and prc1b to promote regeneration of the lost myocardium (middle). In the absence of foxm1 (top), induction of these G₂ and M phase genes is decreased and border zone cardiomyocytes do not proliferate. In the absence of cenpf (bottom), cardiomyocytes may progress through the cell cycle until M phase, when Cenpf protein is required for chromatid separation. These dividing cells likely undergo cytokinetic dysregulation, which results in failed mitosis, generating binucleated cardiomyocytes.