-Catenin activity in the dermal papilla of the hair follicle regulates pigment-type switching

Cutaneous Biology Research Center, Harvard Medical School and Massachusetts General Hospital, Charlestown, MA 02129, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 11/2010; 107(50):21564-9. DOI: 10.1073/pnas.1007326107
Source: PubMed


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.

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    • "To the best of our knowledge, this is the first study to show that ACT extract promotes hair growth through the activation of the Wnt/β-catenin pathway by enhancing β-catenin transcription and possibly by a mitogenic effect on dermal papilla cells. Because the Wnt/β-catenin pathway and β-catenin, in particular, play important roles in hair growth and NPC differentiation, we employed the pTOPFlash and NPC differentiation assays to screen materials for their abilities to activate this pathway (Jiro and Robert, 2000; Ito et al., 2007; David et al., 2010). From the results of these assays, the ACT extract was selected for further studies. "
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