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    Topobiology of human pigmentation: P-cadherin selectively stimulates hair follicle melanogenesis

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    Publication date
    2013
    Author
    Samuelov, L.
    Sprecher, E.
    Sugawara, K.
    Singh, Suman K.
    Tobin, Desmond J.
    Tsuruta, D.
    Bíró, T.
    Kloepper, J.E.
    Paus, R.
    Keyword
    Topobiology; Human Pigmentation; P-Cadherin; Hair Follicles; Hair Follicle Melanogenesis; Mammalian epithelium
    Peer-Reviewed
    Yes
    
    Metadata
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    Abstract
    P-cadherin serves as a major topobiological cue in mammalian epithelium. In human hair follicles (HFs), it is prominently expressed in the inner hair matrix that harbors the HF pigmentary unit. However, the role of P-cadherin in normal human pigmentation remains unknown. As patients with mutations in the gene that encodes P-cadherin show hypotrichosis and fair hair, we explored the hypothesis that P-cadherin may control HF pigmentation. When P-cadherin was silenced in melanogenically active organ-cultured human scalp HFs, this significantly reduced HF melanogenesis and tyrosinase activity as well as gene and/or protein expression of gp100, stem cell factor, c-Kit, and microphthalmia-associated transcription factor (MITF), both in situ and in isolated human HF melanocytes. Instead, epidermal pigmentation was unaffected by P-cadherin knockdown in organ-cultured human skin. In hair matrix keratinocytes, P-cadherin silencing reduced plasma membrane β-catenin, whereas glycogen synthase kinase 3 beta (GSK3β) and phospho-β-catenin expression were significantly upregulated. This suggests that P-cadherin-GSK3β/Wnt signaling is required for maintaining the expression of MITF to sustain intrafollicular melanogenesis. Thus, P-cadherin-mediated signaling is a melanocyte subtype-specific topobiological regulator of normal human pigmentation, possibly via GSK3β-mediated canonical Wnt signaling.
    URI
    http://hdl.handle.net/10454/7143
    Version
    No full-text available in the repository
    Citation
    Samuelov L, Sprecher E, Sugawara K et al (2013) Topobiology of human pigmentation: P-cadherin selectively stimulates hair follicle melanogenesis. Journal of Investigative Dermatology. 133(6): 1591-600.
    Link to publisher’s version
    http://www.nature.com/jid/journal/v133/n6/abs/jid201318a.html
    Type
    Article
    Collections
    Life Sciences Publications

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