REGULATION OF CARDIAC DEVELOPMENT BY RECEPTOR TYROSINE KINASES

The development of a functional heart depends on the coordinated growt h, differentiation, migration, and apoptosis of cell populations of di verse embryological origins. These processes are regulated in part by soluble polypeptide growth factors that exert their effects via bindin g to cell surface receptors with intrinsic tyrosine kinase activity. I n particular, members of this class of receptors and their ligands hav e been shown to regulate the development of distinctive regions of the heart, such as the mesodermally derived cardiac myocyte, the endocard ium, and outflow tract and septa, which depend on cardiac neural crest . The hepatocyte growth factor receptor, c-met the fibroblast growth f actor receptors; and the neuregulin receptors have be en shown to infl uence cardiomyocyte proliferation and/or differentiation. Receptors bi nding to vascular endothelial cell growth factor or angiopoietin have been implicated in the development of the endocardium. Finally, gene-t argeting experiments in the mouse have demonstrated functional roles f or neurotrophins and their cognate trk receptor tyrosine kinases in th e development of outflow tract, septa, and valves that are structures derived from cardiac neural crest. (C) 1998 Elsevier Science Inc.