Molecular cloning of the Xenopus c-met/hepatocyte growth factor receptor and its regional expression during early development.

Abstract

Hepatocyte growth factor (HGF), a ligand for c-Met receptor tyrosine kinase, regulates the cell growth, migration and morphogenesis of a wide variety of cells, and plays important roles in organogenesis in embryos as well as regeneration of organs. HGF is structurally conserved in Xenopus laevis, and the Xenopus HGF gene is expressed in neurula and tailbud embryos. In the present work, we cloned complementary DNA for the Xenopus Met/ HGF receptor and analyzed its expression during embryogenesis. The open reading frame of Xenopus c-met is 4,125 base pairs long and encodes a putative polypeptide of 1,375 amino acids. The deduced amino acid sequences of the Xenopus and human Met proteins are 63% identical, the tyrosine kinase domains in the intracellular regions showing particular homology, over 90% identity in the amino acid sequences between Xenopus and human. During Xenopus embryogenesis, c-met mRNA was expressed at a high level from the gastrula to the neurula stage, while HGF mRNA expression was seen from the early neurula stage. Whole mount in situ hybridization showed that c-met mRNA was specifically localized in the foregut region, mesenchymal tissue of the tailbud, and neural tissues in neurula embryos. Thus, c-Met is a highly conserved molecule in a wide range of species, as is its ligand, HGF. The HGF-Met system may be involved in early multiple organogenesis in Xenopus embryos.