Investigating the Metabolism of Melanocyte Development.

During development, melanocytes undergo a series of cellular and metabolic changes in order to reach a terminally differentiated state. Some of these changes include extensive proliferation, formation of dendritic projections from the cell membrane, and melanin synthesis. Each of these processes is likely to create distinct metabolic needs, however, little work has been done to investigate how the differentiating melanocyte meets these requirements. Previous work in our lab identified that stromal mesenchymal adipocytes are donors of lipids that aids in melanoma progression and metastasis. This raises the question of whether fatty acid metabolism might also play a role in melanocyte development. Additionally, it indicates a need for further investigation into the role of cellular metabolism in both melanocyte differentiation and related diseases. Herein, we performed a chemical screen as a discovery approach using the Sigma Aldrich LOPAC library containing 1280 compounds in T5D zebrafish embryos and validate the primary hits via titration at different developmental time points. Treatment was initiated at 24-hour post fertilization for a 48-hour period at a 10 μM concentration. With this screen we identified a total of fifty compounds which affected melanocyte growth, development, migration pattern, and/or phenotypic appearance in the context of a complete developing organism allowing a more comprehensive analysis. Preliminary data suggest that different pathways such as T-Cell Receptor inhibition, nitric oxide donors and/or sequesters, inhibition of inflammatory responses from macrophages, basophils and mast cells can potentially affect melanocyte development. Together, these findings help us to better understand the details of melanocyte development and further characterization of these pathways will greatly enhance our understanding of the metabolic requirements of these processes and could yield insight into the role of these processes in melanoma and other disease contexts.