Passeron1, T., Valencia1, J.C., Bertolotto2, C., Hoashi1, T., Le Pape1, E., Takahashi1, K., Ballotti2, R., and Hearing1, V.J. 1 1Pigment Cell Biology Section, Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814; and 2Unite 597, Institut National de la Sante et de la Recherche Medicale, Faculte de Medecine, Universite de Nice Sophia–Antipolis, 06103 Nice, France.

This study by researchers from the National Cancer Institute (USA) and the Universite de Nice Sophia–Antipolis (France) demonstrated the ability to use MelanoDerm, one of MatTek’s re-constructed skin models, as a surrogate to assess the effect of UVB radiation on SOX9 expression in human skin in vivo. SOX (SRY type HMG box) proteins are transcription factors that are predominantly known for their roles during development. During melanocyte development from the neural crest, SOX10 regulates microphthalmia-associated transcription factor, which controls a set of genes critical for pigment cell development and pigmentation, including dopachrome tautomerase and tyrosinase. Researchers from the National Cancer Institute (USA) and the Faculte de Medecine, Universite de Nice Sophia–Antipolis report here that another SOX factor, SOX9, is expressed by melanocytes in neonatal and adult human skin and is up-regulated by UVB exposure. MatTek re-constructed skin tissues (MelanoDerm) were used in this study. The researchers demonstrate that this regulation is mediated by cAMP and protein kinase. They also show that agouti signal protein, a secreted factor known to decrease pigmentation, down-regulates SOX9 expression. In adult and neonatal melanocytes, SOX9 regulates microphthalmia-associated transcription factor, dopachrome tautomerase, and tyrosinase promoters, leading to an increase in the expression of these key melanogenic proteins and finally to a stimulation of pigmentation. SOX9 completes the complex and tightly regulated process leading to the production of melanin by acting at a very upstream level. This role of SOX9 in pigmentation emphasizes the poorly understood impact of SOX proteins in adult tissues.


Agouti signal protein, Dopachrome tautomerase, Melanin, MelanoDerm, Melanocyte development, Melanogenic proteins, Microphthalmia-associated transcription factor (MITF), Neural crest, Protein kinase, SOX (SRY type HMG box) proteins, SOX10, SOX9, Transcription factors, Tyrosinase, UVB exposure, cAMP

Request a copy of this paper, click here.