Melanin Transfer in the Epidermis: The Pursuit of Skin Pigmentation Control Mechanisms

The mechanism by which the pigment melanin is transferred from melanocytes to keratinocytes to achieve skin pigmentation remains controversial. Several models emerged in the past decades to explain the transfer process. Here, we review the proposed models for melanin transfer in the skin epidermis, the available evidence supporting each one, and the recent observations made by ours and other groups in favor of the exo/phagocytosis and shed vesicles models. Moreover, we propose that different models could coexist to sustain skin pigmentation under different conditions. Finally, we discuss new questions that ought to be addressed to solve the long-lasting quest for the understanding of how basal skin pigmentation is controlled. This knowledge will allow the emergence of new strategies to treat pigmentary disorders that cause a significant socio-economic burden to patients and healthcare systems worldwide and could also have relevant cosmetic applications.