Role of HGF in Development of CNS Architecture

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Hepatocyte growth factor/scatter factor (HGF/SF) functions as a mitogen, motogen and morphogen for a variety of cultured cells. The genes for HGF/SF and its receptor (the c-met proto-oncogene product) are expressed in many tissues during the embryonic periods and in the adult. HGF/SF is thought to mediate a signal exchange between the mesenchyme and epithelia during mouse development. The mice embryos with a targeted disruption of the HGF/SF gene have severely impaired placentas with markedly reduced numbers of labyrinthine trophoblast cells, and die before birth. The growth of trophoblast cells was stimulated by HGF/SF in vitro, and the HGF/SF activity was released by allantois in primary culture of normal but not mutant embryos. These observations show that HGF/SF is an essential mediator of allantoic mesenchyme-trophoblastic epithelia interaction required for placental organogenesis. To investigate further role for HGF in later stage of development of central nervous system (CNS) architecture, the placental defect of the mutant embryos was rescued by tetraploid aggregation methodology. Using these rescued mutants, histological analysis of CNS are under investigation.