The Origins of Melanocyte Heterogeneity in Health and Disease

How embryonic cells make cell fate decisions to give rise to adult tissues is a fundamental question in developmental biology with significant implications for understanding genetic disease. Our collaborative team, including a network of discovery and clinical scientists, will address this question in the context of the melanocyte lineage that gives rise to the pigmented cells found in our skin and throughout the body. We hypothesise that cells of multiple distinct known and unknown origins give rise to melanocytes, and that the origins contribute to variation in melanocytic disease in humans, including distinct subtypes of melanoma. Harnessing advanced zebrafish and human cell models, we will apply genomic technologies and experimental perturbation experiments to build the first cellular map of the origins of all melanocytes in a vertebrate, from embryo to the adult. We will reveal the gene regulatory circuitries that function as cellular “guides” through this living map, and that underpin melanocyte health and disease states. Our Team’s discoveries have the potential to alter our understanding of how melanocytes pigment our body, and how the embryological origin of cells influences disease.