Document Detail

Analysis of melanocyte precursors in Nf1 mutants reveals that MGF/KIT signaling promotes directed cell migration independent of its function in cell survival.
MedLine Citation:
PMID:  11401406     Owner:  NLM     Status:  MEDLINE    
Neural crest-derived melanocyte precursors (MPs) in avian and murine embryos emerge from the dorsal neural tube into a migration staging area (MSA). MPs subsequently migrate from the MSA on a dorsolateral pathway between the dermamyotome and the overlying epithelium. In mouse embryos, MPs express the receptor tyrosine kinase, KIT, and require its cognate ligand, Mast cell growth factor (MGF), for survival and differentiation. Prior to the onset of MP migration, MGF is expressed on the dorsolateral pathway at some distance from cells in the MSA and appears to be required for normal MP development. To learn if MGF is required solely for MP survival on this pathway, or if it also provides directional cues for migration, we uncoupled survival from chemoattractive or motogenic functions of this ligand using mice that carry a targeted mutation at the Neurofibromin (Nf1) locus and consequently lack RAS-GAP function. We show that Nf1-mutant MPs survive in the absence of MGF in vitro and in vivo and that Nf1-mutant MPs disperse normally on the lateral migration pathway in the presence of MGF. In contrast, Nf1-mutant MPs persist in the location of the MSA but are not observed on the lateral migration pathway in double-mutant mice that also lack MGF. We conclude that MGF/KIT function provides a signal required for directed migration of the MPs on the lateral pathway in vivo, independent of its function in survival. We further suggest that the MGF mediates MP migration through a signaling pathway that does not involve RAS.
B Wehrle-Haller; M Meller; J A Weston
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Developmental biology     Volume:  232     ISSN:  0012-1606     ISO Abbreviation:  Dev. Biol.     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-06-12     Completed Date:  2001-06-28     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  471-83     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Academic Press.
Institute of Neuroscience, University of Oregon, Eugene, Oregon 97403-1254, USA.
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MeSH Terms
Cell Differentiation
Cell Movement / physiology*
Cell Survival
Melanocytes / cytology,  physiology*
Mice, Inbred C57BL
Mice, Knockout
Models, Biological
Nerve Tissue Proteins / genetics*,  physiology*
Neural Crest / cytology
Neurofibromin 1
Oncogene Proteins / physiology*
Proto-Oncogene Proteins c-kit
Signal Transduction
Stem Cell Factor / genetics,  physiology*
Stem Cells / cytology,  physiology
ras GTPase-Activating Proteins / physiology
Grant Support
Reg. No./Substance:
0/Nerve Tissue Proteins; 0/Neurofibromin 1; 0/Oncogene Proteins; 0/Stem Cell Factor; 0/ras GTPase-Activating Proteins; EC Proteins c-kit

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