ABSTRACT
Pigmentation serves various purposes such as protection, camouflage, or attraction. In the skin epidermis, melanocytes react to certain environmental signals with melanin production and release, thereby ensuring photo-protection. For this, melanocytes acquire a highly polarized and dendritic architecture that facilitates interactions with surrounding keratinocytes and melanin transfer. How the morphology and function of these neural crest-derived cells is regulated remains poorly understood. Here, using mouse genetics and primary cell cultures, we show that conserved proteins of the mammalian Par3-aPKC polarity complex are required for epidermal pigmentation. Melanocyte-specific deletion of Par3 in mice caused skin hypopigmentation, reduced expression of components of the melanin synthesis pathway, and altered dendritic morphology. Mechanistically, Par3 was necessary downstream of α-melanocyte stimulating hormone (α-MSH) to elicit melanin production. Strikingly, pharmacologic activation of MITF using a salt-inducible kinase inhibitor was sufficient to restore melanocyte differentiation and skin pigmentation in the absence of Par3. This data reveals a central role of polarity proteins in transmitting external pigment-inducing signals through the α-MSH/Mc1R/MITF ‘tanning pathway’, exposing unexpected links between polarity signaling and melanogenesis with new insights for pigment cell biology.
Competing Interest Statement
The authors have declared no competing interest.
