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

ArticleinProceedings of the National Academy of Sciences 107(50):21564-9 · November 2010with30 Reads
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.
    • "Ablation of β-catenin in Corin+ DP cells causes reduced proliferation of matrix keratinocytes, resulting in early catagen and blockage of entry into a new hair growth cycle [17] . Surprisingly, however, when a stabilized form of β-catenin (Ctnnb1 (Ex3)fl/+ ) was overexpressed in Corin+ DP cells, no change in postnatal hair cycling was observed [18]. Similarly, expression of the same stabilized β-catenin protein in CD133+ DP cells did not result in any phenotype in postnatal hair growth except for an increase in the DP size [19]. "
    [Show abstract] [Hide abstract] ABSTRACT: The hair follicle dermal papilla (DP) contains a unique prominin-1/CD133-positive (CD133+) cell subpopulation, which has been shown to possess hair follicle-inducing capability. By assaying for endogenous CD133 expression and performing lineage tracing using CD133-CreER <sup> T2 </sup>; ZsGreen1 reporter mice, we find that CD133 is expressed in a subpopulation of DP cells during the growth phase of the murine hair cycle (anagen), but is absent at anagen onset. However, how CD133+ DP cells interact with keratinocytes to induce hair regenerative growth remains unclear. Wnt/β-catenin has long been recognized as a major signaling pathway required for hair follicle morphogenesis, development, and regeneration. Nuclear Wnt/β-catenin activity is observed in the DP during the hair growth phase. Here we show that induced expression of a stabilized form of β-catenin in CD133+ DP cells significantly accelerates spontaneous and depilation-induced hair growth. H
    Full-text · Article · Jul 2016
    • "In early embryogenesis, before E16.5, -catenin expression in fibroblasts is required for the formation of the dorsal and ventral dermis, while ectopic -catenin activation increases fibroblast density and disturbs epidermal morphogenesis (Atit et al., 2006; Chen et al., 2012; Ohtola et al., 2008). In late embryonic dermis, when fibroblast lineages have been established, altered -catenin activity in the DP causes defects in HF growth, cycling, and pigmentation but does not cause HF loss (Enshell-Seijffers et al., 2010a; 2010b). In contrast, -catenin activation in postnatal ventral dermis Development @BULLET Advance article fibroblasts causes fibrosis in the adipocyte layer (Mastrogiannaki et al., 2016; Hamburg and Atit, 2012; Hamburg-Shields et al., 2015), supporting our observations in older unwounded skin (Fig.7B). "
    [Show abstract] [Hide abstract] ABSTRACT: New hair follicles (HF) do not form in adult mammalian skin unless epidermal Wnt signalling is activated genetically or within large wounds. To understand the postnatal loss of hair forming ability we made small (2mm diameter) circular wounds and monitored HF formation at the wound site. At P2 new follicles formed in back skin, but follicle formation was markedly decreased by P21. Neonatal tail also formed wound-associated follicles, albeit in smaller numbers. Postnatal loss of HF neogenesis did not correlate with wound closure rate but with reduction in Lrig1-positive papillary fibroblasts in wounds. Comparative gene expression profiling of back and tail dermis at P1 and dorsal fibroblasts at P2 and P50 showed a correlation between loss of HF formation and decreased expression of genes associated with proliferation and Wnt/β-catenin activity. Between P2 and P50 fibroblast density declined throughout the dermis and clones of fibroblasts became more dispersed. This correlated with a decline in fibroblasts expressing a TOPGFP reporter of Wnt activation. Surprisingly, between P2 and P50 there was no difference in fibroblast proliferation at the wound site but Wnt signalling was highly upregulated in healing dermis of P21 compared to P2 mice. Postnatal β-catenin ablation in fibroblasts promoted HF regeneration in neonatal and adult mouse wounds while β-catenin activation reduced HF regeneration in neonatal wounds. Our data support a model whereby postnatal loss of hair forming ability in wounds reflects elevated dermal Wnt/β-catenin activation in the wound bed, increasing the abundance of fibroblasts that are unable to induce HF formation.
    Full-text · Article · Jun 2016
    • "This highlights a previously unappreciated connectivity between mesenchymal compartments and identifies a physical substrate by which hfDSCs and their progeny within the DP communicate with more remote or functionally distinct regions of the DP, matrix cells and melanocytes, as opposed to local communication between neighboring cells. Indeed, a modulatory role for DP cells on melanocytes via b-catenin signaling has already been reported (Enshell-Seijffers et al., 2010). Their unique location and close proximity to DP cells (at all stages of the hair cycle) may also allow hfDSCs to act as cellular intermediate transmitting extrafollicular signals into the DP. "
    [Show abstract] [Hide abstract] ABSTRACT: The dermal papilla (DP) provide instructive signals required to activate epithelial progenitors and initiate hair follicle regeneration. DP cell numbers fluctuate over the hair cycle, and hair loss is associated with gradual depletion/atrophy of DP cells. How DP cell numbers are maintained in healthy follicles remains unclear. We performed in vivo fate mapping of adult hair follicle dermal sheath (DS) cells to determine their lineage relationship with DP and found that a subset of DS cells are retained following each hair cycle, exhibit self-renewal, and repopulate the DS and the DP with new cells. Ablating these hair follicle dermal stem cells and their progeny retarded hair regrowth and altered hair type specification, sug- gesting that they function to modulate normal DP function. This work identifies a bipotent stem cell within the adult hair follicle mesenchyme and has important implications toward restoration of hair growth after injury, disease, and aging.
    Full-text · Article · Dec 2014
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