title: Hepatocyte growth factor acts as a mitogen and chemoattractant for postnatal subventricular zone-olfactory bulb neurogenesis.
abstract: Neural progenitor cells persist throughout life in the forebrain subventricular zone (SVZ). They generate neuroblasts that migrate to the olfactory bulb and differentiate into interneurons, but mechanisms underlying these processes are poorly understood. Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic factor that influences cell motility, proliferation and morphogenesis in neural and non-neural tissues. HGF and its receptor, c-Met, are present in the rodent SVZ-olfactory bulb pathway. Using in vitro neurogenesis assays and in vivo studies of partially HGF-deficient mice, we find that HGF promotes SVZ cell proliferation and progenitor cell maintenance, while slowing differentiation and possibly altering cell fate choices. HGF also acts as a chemoattractant for SVZ neuroblasts in co-culture assays. Decreased HGF signaling induces ectopic SVZ neuroblast migration and alters the timing of migration to the olfactory bulb. These results suggest that HGF influences multiple steps in postnatal forebrain neurogenesis. HGF is a mitogen for SVZ neural progenitors, and regulates their differentiation and olfactory bulb migration.
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Tsu-Wei
authors.initials: TW
authors.lastname: Wang
authors.forename: Huailin
authors.initials: H
authors.lastname: Zhang
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Gyetko
authors.forename: Jack M
authors.initials: JM
authors.lastname: Parent
mesh_terms: D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000378:metabolism*; D002522:Chlorocebus aethiops; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008934:Mitogens / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology* / Q000196:embryology*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: D002630:Chemotactic Factors; D008934:Mitogens; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met