EXPRESSION AND FUNCTIONAL INTERACTION OF HEPATOCYTE GROWTH FACTOR-SCATTER FACTOR AND ITS RECEPTOR C-MET IN MAMMALIAN BRAIN

Hepatocyte growth factor-scatter factor (HGF-SF) is a pleiotropic cyto kine with mito-, morpho-, and motogenic effects on a variety of epithe lial and endothelial cells. HGE-SF activity is mediated by the c-met p rotooncogene, a membrane-bound tyrosine kinase. Here, we demonstrate t hat both genes are expressed in developing and adult mammalian brains. HGF-SF mRNA is localized in neurons, primarily in the hippocampus, th e cortex, and the granule cell layer of the cerebellum, and it is also present at high levels in ependymal cells, the chorioid plexus, and t he pineal body. c-met is expressed in neurons, preferentially in the C A-1 area of the hippocampus, the cortex, and the septum, as well as in the pons. In the embryonic mouse, brain HGF-SF and c-met are expresse d as early as days 12 and 13, respectively. Neuronal expression of HGF -SF is evolutionary highly conserved and detectable beyond the mammali an class. Incubation of septal neurons in culture with HGF-SF leads to a rapid increase of c-fos mRNA levels. The results demonstrate the pr esence of a novel growth factor-tyrosine kinase signaling system in th e brain, and they suggest that HGF-SF induces a functional response in a neuronal subpopulation of developing and adult CNS.