Regulation of cardiac development by receptor tyrosine kinases

The development of a functional heart depends on the coordinated growth, differentiation, migration, and apoptosis of cell populations of diverse embryological origins. These processes are regulated in part by soluble polypeptide growth factors that exert their effects via binding to cell surface receptors with intrinsic tyrosine kinase activity. In particular, members of this class of receptors and their ligands have been shown to regulate the development of distinctive regions of the heart, such as the mesodermally derived cardiac myocyte, the endocardium, and outflow tract and septa, which depend on cardiac neural crest. The hepatocyte growth factor receptor, c-met the fibroblast growth factor receptors; and the neuregulin receptors have been shown to influence cardiomyocyte proliferation and/or differentiation. Receptors binding to vascular endothelial cell growth factor or angiopoietin have been implicated in the development of the endocardium. Finally, gene-targeting experiments in the mouse have demonstrated functional roles for neurotrophins and their cognate trk receptor tyrosine kinases in the development of outflow tract, septa, and valves that are structures derived from cardiac neural crest.