title: Beta-catenin activity in the dermal papilla of the hair follicle regulates pigment-type switching.
abstract: The switch between black and yellow pigment is mediated by the interaction between Melanocortin receptor 1 (Mc1r) and its antagonist Agouti, but the genetic and developmental mechanisms that modify this interaction to obtain different coat color in distinct environments are poorly understood. Here, the role of Wnt/β-catenin signaling in the regulation of pigment-type switching was studied. Loss and gain of function of β-catenin in the dermal papilla (DP) of the hair follicle results in yellow and black animals, respectively. β-Catenin activity in the DP suppresses Agouti expression and activates Corin, a negative regulator of Agouti activity. In addition, β-catenin activity in the DP regulates melanocyte activity by a mechanism that is independent of both Agouti and Corin. The coordinate and inverse regulation of Agouti and Corin renders pelage pigmentation sensitive to changes in β-catenin activity in the DP that do not alter pelage structure. As a result, the signals that specify two biologically distinct quantitative traits are partially uncoupled despite their common regulation by the β-catenin pathway in the same cells.
authors.affiliation: Cutaneous Biology Research Center, Harvard Medical School and Massachusetts General Hospital, Charlestown, MA 02129, USA. david.enshell@cbrc2.mgh.harvard.edu
authors.forename: David
authors.initials: D
authors.lastname: Enshell-Seijffers
authors.forename: Catherine
authors.initials: C
authors.lastname: Lindon
authors.forename: Eleanor
authors.initials: E
authors.lastname: Wu
authors.forename: Makoto M
authors.initials: MM
authors.lastname: Taketo
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Morgan
mesh_terms: D054366:Agouti Signaling Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D018859:Hair Follicle / Q000378:metabolism*; D008544:Melanocytes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010858:Pigmentation / Q000502:physiology*; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D054366:Agouti Signaling Protein; D044102:Receptor, Melanocortin, Type 1; D051153:Wnt Proteins; D051176:beta Catenin; C485617:Corin protein, mouse; D012697:Serine Endopeptidases