The mammalian heart has a transient regenerative ability during the neonatal stage. This ability depends on the replicative potential of endogenous cardiomyocytes; however, the underlying transcriptional network that controls cardiomyocyte replication during neonatal heart regeneration remains poorly understood. In this issue (see p. ), Bin Zhou and colleagues investigate the role of GATA4 – a transcription factor that is crucial for cardiac specification and development – in cardiomyocyte turnover and neonatal heart repair. The authors utilised cryoinjury and apex resection models in a neonatal transgenic mouse in which they could control expression of GATA4 specifically in the cardiomyocytes. Following injury, the authors observed severely compromised ventricular function in Gata4-ablated mice, which was accompanied by reduced cardiomyocyte replication and hypertrophy. Importantly, the authors identified FGF16 as a downstream effector of the Gata4-ablated phenotype, and showed that cardiac-specific overexpression of FGF16 promoted cardiomyocyte replication and improved heart function after injury. These data identify GATA4 and FGF16 as important mediators of neonatal heart repair and bring hope for the possibility of paracrine-mediated repair in the adult heart.
