During mid-gestation in the mouse, cardiogenesis switches from patterning processes to growth and chamber formation. Disruption of this transition can lead to a variety of congenital heart diseases, and, on , Chen et al. shed some light on the mechanisms underlying these defects. During the mid-gestation transition, the trabecular myocardium proliferates to generate myocytes that contribute the future ventricular septum, papillary muscles and conduction system. It has been shown previously that mice lacking FK506-binding protein 12 die because of an overproduction of ventricular trabeculae, and that BMP10, which is normally transiently expressed in the trabecular myocardium, is upregulated in these hypertrabeculated hearts. Chen and colleagues have found that in the myocardium of mice lacking BMP10, the negative cell-cycle regulator p57kip2 is upregulated and that cardiomyocyte proliferation is reduced. Furthermore, cardiogenic factors (e.g. NKX2.5 and MEF2C) are downregulated. They conclude that BMP10 is a positive cardiomyocyte growth signal that, together with negative cell-cycle regulators, orchestrates the balance between proliferation and terminal differentiation.
