Topobiology of Human Pigmentation: P-Cadherin Selectively Stimulates Hair Follicle Melanogenesis.

Samuelov, L. and Sprecher, E. and Sugawara, K. and Singh, S.K. and Tobin, D.J. and Bíró, Tamás (2013) Topobiology of Human Pigmentation: P-Cadherin Selectively Stimulates Hair Follicle Melanogenesis. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 133 (6). pp. 1591-1600. ISSN 0022-202X

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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. Since 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 beta-catenin, while glycogen synthase kinase 3 beta (GSK3beta) and phospho-beta-catenin expression were significantly upregulated. This suggests that P-cadherin-GSK3beta/Wnt signaling is required for maintaining 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 GSK3beta-mediated canonical Wnt signaling.Journal of Investigative Dermatology accepted article preview online, 18 January 2013; doi:10.1038/jid.2013.18.

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