An integrated model for melanocyte‐specific gene expression and melanogenesis

Abstract

AbstractThe steady increase in the incidence of cutaneous (skin) malignant melanoma worldwide generates the necessity to understand the key molecular events underlying melanogenesis and melanoma. Melanogenesis has two main stages: immediate pigmentation occurs through the redistribution of pigment‐containing melanosomes to the dendrites of melanocytes, and subsequently to the surrounding keratinocytes, without the need for any new melanin synthesis. The effect is therefore subtle and transient. Delayed and sustained tanning, however, requires (a) an increase in melanocyte number and dendricity, (b) an increase in melanosome number, and (c) an increase in melanin content. This computer‐based model focuses on the sustained eumelanin (black/brown pigment) production through melanocyte‐specific gene expression in response to external stimulus. We find in our model that high levels of melanin can be reached within an hour of stimulation. Furthermore we successfully show metabolic downregulation of pigment synthesis through employing in our simulations an experimentally‐described inhibitor for melanogenic enzymes. We see this model as a starting point for in silico drug screening for skin lightening agents, sun‐tanning agents, and eventually for anti‐melanoma agents that are under development.