ACTIVATION OF MET TYROSINE KINASE BY HEPATOCYTE GROWTH-FACTOR IS ESSENTIAL FOR INTERNAL ORGANOGENESIS IN XENOPUS EMBRYO

Hepatocyte growth factor (HGF) specifically activates Met tyrosine kin ase receptor, leading to mitogenic, motogenic, and morphogenic respons es in a wide variety of cells. To know a role of HGF in Xenopus embryo genesis, loss-of-function mutation was introduced by dominant expressi on of truncated tyrosine kinase-negative Met. When tyrosine kinase-neg ative Met mRNA was micro-injected into two-cell to eight-cell stages X enopus embryos, the liver development was mostly impaired and structur es of pronephros and the gut were grossly underdeveloped in the restri cted, late stage of development. These results strongly suggest that f unctional coupling between HGF and Met is essential for the developmen t of internal organs originated from primitive gut and possibly involv ed in embryonic skeletogenesis. Together with developmental abnormalit y in mice mutated with HGF or Met gene, essential role of HGF for live r development is highly conserved from amphibian to mammalian species. (C) 1997 Academic Press.