An Unexpected Switch: Regulation of Cardiomyocyte Proliferation by the Homeobox Gene Meis1

The mammalian heart has a limited capacity for regeneration after damage. In contrast, teleost fish and urodelian amphibians readily regenerate even large cardiac defects. One of the central differences between species capable and incapable of efficient heart regeneration is the ability to reinitiate cardiomyocyte proliferation. The importance of cardiomyocyte proliferation for heart regeneration is underscored by the finding that fetal and neonatal mouse hearts efficiently regenerate until efficient proliferation of cardiomyocytes ends during the first week after birth.1,2 In a recent article in Nature, Mahmoud et al3 now reported that constitutive and inducible cardiomyocyte-specific deletion of the homeobox gene Meis1 lifts the ban on cardiomyocyte proliferation in adult hearts of mice. Meis1 deficiency increases cardiomyocyte numbers and heart/body weight ratio while maintaining cardiomyocyte size and heart function. Overexpression of Meis1, however, blocks cardiomyocyte proliferation and heart regeneration after myocardial infarction in newborn mice, suggesting that Meis1 acts as a critical driver of cell cycle arrest in the postnatal myocardium. © 2013 American Heart Association, Inc.