Congenital heart disease – the commonest type of human birth defect – is the result of abnormal early heart development. In this issue, two papers investigate how opposing fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) signals control the differentiation of the secondary heart field (SHF) and anterior heart field (AHF) cardiac progenitors during early vertebrate heart development.
On p. , by isolating and culturing chick SHF mesoderm, which forms the myocardium and smooth muscle of the heart's arterial pole (the outflow region of the heart), Mary Hutson and colleagues show that this tissue contains stem cells that can differentiate into myocardium, smooth muscle and endothelial cells. By treating SHF (arterial pole) progenitor cultures with combinations of growth factors and inhibitors, the researchers show that BMP promotes myocardial differentiation but not proliferation of the arterial pole progenitors, whereas FGF promotes their proliferation and smooth muscle cell differentiation but inhibits myocardial differentiation. These and other results indicate that myocardial differentiation of the SHF progenitors requires BMP signalling and downregulation of the FGF/ERK pathway and suggest that the FGF pathway maintains the SHF stem cell pool early but promotes smooth muscle cell differentiation later.
On p. , Eldad Tzahor and colleagues provide further insights into how opposing BMP and FGF signals regulate cardiogenesis by studying the differentiation of chick AHF progenitors, which contribute to the right ventricle and to the arterial pole. By perturbing signalling pathways in vitro and in vivo, the researchers show that, as in SHF progenitors, BMP promotes myocardial differentiation of AHF progenitors by blocking FGF/ERK signalling and that FGF signalling prevents their premature myocardial differentiation. They also show that BMP4 induces the expression of several neural crest-related genes and that cranial neural crest cells are required for BMP-dependent myocardial differentiation of the AHF progenitors. Thus, Tzahor and colleagues suggest, BMP and FGF signalling pathways coordinate the balance between the proliferation and differentiation of cardiac progenitors in the AHF through regulatory loops that act in multiple tissues.
