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Agouti signaling protein and other factors modulating differentiation and proliferation of immortal melanoblasts
Author(s) -
Sviderskaya Elena V.,
Hill Simon P.,
Balachandar Divya,
Barsh Gregory S.,
Bennett Dorothy C.
Publication year - 2001
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.1153
Subject(s) - biology , melanocyte , melanocortin 1 receptor , melanocortin , cellular differentiation , melanocortin receptor , microbiology and biotechnology , embryonic stem cell , melanocyte stimulating hormone , cell culture , receptor , cell growth , signal transduction , endocrinology , gene , genetics , allele , melanoma
The melanocyte lineage potentially forms an attractive model system for studies in cell differentiation, developmental genetics, cell signaling, and melanoma, because differentiated cells produce the visible pigment melanin. Immortal lines of murine melanoblasts (melanocyte precursors) have been described previously, but induction of differentiation involved a complex culture system with keratinocyte feeder cells. Here we describe conditions for both growth and induced differentiation of the melanoblast line melb‐a, without feeder cells, and analyze factors that directly control proliferation and differentiation of these pure melanoblasts. Several active factors are products of developmental and other coat color genes, including stem cell factor (SCF), melanocyte‐stimulating hormone (αMSH), and agouti signaling protein (ASP), a natural antagonist at the MSH receptor (melanocortin 1 receptor, MC1R) encoded by the agouti gene. A stable analog of αMSH (NDP‐MSH) stimulated differentiation and inhibited growth. ASP in excess inhibited both effects of NDP‐MSH, that is, ASP could inhibit pigmentation and stimulate growth. These effects provide an explanation for the interactions in mice of melanocyte developmental mutations with yellow agouti and Mc1r alleles, and a role for embryonic expression patterns of ASP. © 2001 Wiley‐Liss, Inc.