PMID- 10193678
OWN - NLM
STAT- MEDLINE
DCOM- 19990609
LR  - 20220321
IS  - 0893-5785 (Print)
IS  - 0893-5785 (Linking)
VI  - 12
IP  - 1
DP  - 1999 Feb
TI  - Hepatocyte growth factor/scatter factor-MET signaling in neural crest-derived 
      melanocyte development.
PG  - 13-21
AB  - 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.
FAU - Kos, L
AU  - Kos L
AD  - Laboratory for Genetic Disease Research, National Human Genome Research 
      Institute, National Institutes of Health, Bethesda, Maryland 20892-4472, USA.
FAU - Aronzon, A
AU  - Aronzon A
FAU - Takayama, H
AU  - Takayama H
FAU - Maina, F
AU  - Maina F
FAU - Ponzetto, C
AU  - Ponzetto C
FAU - Merlino, G
AU  - Merlino G
FAU - Pavan, W
AU  - Pavan W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Denmark
TA  - Pigment Cell Res
JT  - Pigment cell research
JID - 8800247
RN  - 0 (Stem Cell Factor)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/drug effects
MH  - Cell Division
MH  - Cells, Cultured
MH  - Embryo, Mammalian/drug effects
MH  - Gestational Age
MH  - Hepatocyte Growth Factor/genetics/*metabolism/pharmacology
MH  - Melanocytes/drug effects/*physiology
MH  - Mice
MH  - Mice, Transgenic
MH  - Neural Crest/*cytology/*embryology/metabolism
MH  - Proto-Oncogene Proteins c-met/*metabolism
MH  - Signal Transduction/*physiology
MH  - Stem Cell Factor/metabolism/pharmacology
EDAT- 1999/04/08 00:00
MHDA- 1999/04/08 00:01
CRDT- 1999/04/08 00:00
PHST- 1999/04/08 00:00 [pubmed]
PHST- 1999/04/08 00:01 [medline]
PHST- 1999/04/08 00:00 [entrez]
AID - 10.1111/j.1600-0749.1999.tb00503.x [doi]
PST - ppublish
SO  - Pigment Cell Res. 1999 Feb;12(1):13-21. doi: 10.1111/j.1600-0749.1999.tb00503.x.