The functions of HGF/SF and its receptor, the c-Met tyrosine kinase, in mammalian development.

Abstract

Hepatocyte growth factor/scatter factor (HGF/SF) can induce epithelial-mesenchymal conversion of epithelial cells in culture, with the dissociated cells becoming highly motile. The signal given by HGF/SF is mediated by its specific receptor, the c-Met tyrosine kinase. Targeted mutations in the mouse have demonstrated that HGF/SF and c-Met take over functions in development of the placenta, liver and skeletal muscle. During development of skeletal muscle, the receptor and its ligand control migration of myogenic precursor cells in the embryo. These myogenic precursors undergo an epithelial-mesenchymal conversion and detach from the dermomyotome of the somite. They then migrate to different sites in the embryo where they terminally differentiate to form skeletal muscle. Mutations in the HGF/SF or c-met genes abolish emigration of myogenic precursor cells. As a consequence, skeletal muscle groups that derive from migrating cells do not form. Ectopic application of HGF/SF in the chick embryo induces epithelial-mesenchymal conversion and emigration of dermomyotomal cells. Moreover, the expression patterns of HGF/SF and c-Met in the mouse embryo are in accordance with a function of HGF/SF in the induction of epithelial-mesenchymal conversion and the generation of migrating myogenic precursor cells in vivo. The pattern suggests additional roles during the migratory process, which will be discussed.