RRC ID 6002
Author Aoki H, Yamada Y, Hara A, Kunisada T.
Title Two distinct types of mouse melanocyte: differential signaling requirement for the maintenance of non-cutaneous and dermal versus epidermal melanocytes.
Journal Development
Abstract Unlike the thoroughly investigated melanocyte population in the hair follicle of the epidermis, the growth and differentiation requirements of the melanocytes in the eye, harderian gland and inner ear - the so-called non-cutaneous melanocytes - remain unclear. In this study, we investigated the in vitro and in vivo effects of the factors that regulate melanocyte development on the stem cells or the precursors of these non-cutaneous melanocytes. In general, a reduction in KIT receptor tyrosine kinase signaling leads to disordered melanocyte development. However, melanocytes in the eye, ear and harderian gland were revealed to be less sensitive to KIT signaling than cutaneous melanocytes. Instead, melanocytes in the eye and harderian gland were stimulated more effectively by endothelin 3 (ET3) or hepatocyte growth factor (HGF) signals than by KIT signaling, and the precursors of these melanocytes expressed the lowest amount of KIT. The growth and differentiation of these non-cutaneous melanocytes were specifically inhibited by antagonists for ET3 and HGF. In transgenic mice induced to express ET3 or HGF in their skin and epithelial tissues from human cytokeratin 14 promoters, the survival and differentiation of non-cutaneous and dermal melanocytes, but not epidermal melanocytes, were enhanced, apparently irrespective of KIT signaling. These results provide a molecular basis for the clear discrimination between non-cutaneous or dermal melanocytes and epidermal melanocytes, a difference that might be important in the pathogenesis of melanocyte-related diseases and melanomas.
Volume 136(15)
Pages 2511-21
Published 2009-8-1
DOI 10.1242/dev.037168
PII dev.037168
PMID 19553284
MeSH Animals Cornea / cytology Cornea / drug effects Dermis / cytology* Dermis / drug effects Dermis / metabolism* Endothelin-3 / metabolism Epidermal Cells* Epidermis / drug effects Epidermis / metabolism* Flow Cytometry Harderian Gland / cytology Harderian Gland / drug effects Harderian Gland / embryology Hepatocyte Growth Factor / metabolism Melanocytes / classification* Melanocytes / cytology Melanocytes / enzymology Melanocytes / metabolism* Mice Mice, Transgenic Mutation / genetics Oligopeptides / pharmacology Phenotype Pigmentation / drug effects Piperidines / pharmacology Proto-Oncogene Proteins c-kit / metabolism Signal Transduction* / drug effects Stem Cell Factor / metabolism Stem Cells / cytology Stem Cells / drug effects Stem Cells / metabolism
IF 5.763
Times Cited 59
Mice C57BL/6-Tg(CAG-EGFP)C14-Y01-FM131Osb