title: Hepatocyte growth factor/scatter factor-MET signaling in neural crest-derived melanocyte development.
abstract: The mechanisms governing development of neural crest-derived melanocytes, and how alterations in these pathways lead to hypopigmentation disorders, are not completely understood. Hepatocyte growth factor/scatter factor (HGF/SF) signaling through the tyrosine-kinase receptor, MET, is capable of promoting the proliferation, increasing the motility, and maintaining high tyrosinase activity and melanin synthesis of melanocytes in vitro. In addition, transgenic mice that ubiquitously overexpress HGF/SF demonstrate hyperpigmentation in the skin and leptomenigenes and develop melanomas. To investigate whether HGF/ SF-MET signaling is involved in the development of neural crest-derived melanocytes, transgenic embryos, ubiquitously overexpressing HGF/SF, were analyzed. In HGF/SF transgenic embryos, the distribution of melanoblasts along the characteristic migratory pathway was not affected. However, additional ectopically localized melanoblasts were also observed in the dorsal root ganglia and neural tube, as early as 11.5 days post coitus (p.c.). We utilized an in vitro neural crest culture assay to further explore the role of HGF/SF-MET signaling in neural crest development. HGF/SF added to neural crest cultures increased melanoblast number, permitted differentiation into pigmented melanocytes, promoted melanoblast survival, and could replace mast-cell growth factor/Steel factor (MGF) in explant cultures. To examine whether HGF/SF-MET signaling is required for the proper development of melanocytes, embryos with a targeted Met null mutation (Met-/-) were analysed. In Met-/- embryos, melanoblast number and location were not overtly affected up to 14 days p.c. These results demonstrate that HGF/SF-MET signaling influences, but is not required for, the initial development of neural crest-derived melanocytes in vivo and in vitro.
authors: Laboratory for Genetic Disease Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-4472, USA.
authors: L
authors: L
authors: Kos
authors: A
authors: A
authors: Aronzon
authors: H
authors: H
authors: Takayama
authors: F
authors: F
authors: Maina
authors: C
authors: C
authors: Ponzetto
authors: G
authors: G
authors: Merlino
authors: W
authors: W
authors: Pavan
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000187:drug effects; D005865:Gestational Age; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008544:Melanocytes / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009432:Neural Crest / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D019089:Stem Cell Factor / Q000378:metabolism / Q000494:pharmacology
chemical_list: D019089:Stem Cell Factor; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met