An explanation for the mysterious distribution of melanin in human skin: a rare example of asymmetric (melanin) organelle distribution during mitosis of basal layer progenitor keratinocytes. (12th September 2018)

• Record Type: Journal Article
• Authors: Joly‐Tonetti, N.; Wibawa, J.I.D.; Bell, M.; Tobin, D.J.
• Is Part Of: British journal of dermatology. Volume 179:Number 5(2018)
• Page Start: 1115
• Page End: 1126
• Publication Date: 2018-09-12
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.16926
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: Background: Melanin is synthesized by melanocytes in the basal layer of the epidermis. When transferred to surrounding keratinocytes melanin is the key ultraviolet radiation‐protective biopolymer responsible for skin pigmentation. Most melanin is observable in the proliferative basal layer of the epidermis and only sparsely distributed in the stratifying/differentiating epidermis. The latter has been explained as 'melanin degradation' in suprabasal layers. Objectives: To re‐evaluate the currently accepted basis for melanin distribution in human epidermis and to discover whether this pattern is altered after a regenerative stimulus. Methods: Normal epidermis of adult human skin, at rest and after tape‐stripping, was analysed by a range of (immuno)histochemical and high‐resolution microscopy techniques. In vitro models of melanin granule uptake by human keratinocytes were attempted. Results: We propose a different fate for melanin in the human epidermis. Our evidence indicates that the bulk of melanin is inherited only by the nondifferentiating daughter cell postmitosis in progenitor keratinocytes via asymmetric organelle inheritance. Moreover, this preferred pattern of melanin distribution can switch to a symmetric or equal daughter cell inheritance mode under conditions of stress, including regeneration. Conclusions: In this preliminary report, we provide a plausible and histologically supported explanation for how human skin pigmentation is efficiently organized in the epidermis. Steady‐state epidermis pigmentation may involve much less redox‐sensitive melanogenesis than previously thought, and at least some premade melanin may be available for reuse. The epidermal melanin unit may be an excellent example with which to study organelle distribution via asymmetric or symmetric inheritance in response to microenvironment and tissue demands. Abstract : What's already known about this topic? Synthesized by the melanocyte, melanin pigment is transferred to surrounding keratinocytes, where it commonly assembles as ultraviolet radiation‐protective supranuclear caps in the basal layer. Melanin appears markedly decreased in the epidermis layers above the proliferative basal layer. A clear explanation of this classical histological appearance has been elusive, except via the unproven dogma of 'melanin degradation' in the suprabasal epidermis. What does this study add? We propose that the restriction of the vast majority of melanin to the stratum basale results from an asymmetric distribution of melanin granules to the nondifferentiating daughter progeny cell during keratinocyte mitosis. If required, this shifts to a symmetric mode of melanin inheritance into both daughter cells for more general melanin distribution throughout the epidermis. This study reports a rare example of asymmetric organelle distribution during mitosis in human cells. What is the translational message? A greater understanding of how melanin is processed within proliferating vs. differentiating keratinocytes in the human epidermis could lead to improved treatment of pigmentary disorders. Respond to this article Plain language summary available online