Research Project
9730882
Pigment variation is a powerful model to understand the genetic and evolutionary forces that generate phenotypic diversity. Among most vertebrates, this variation is caused by differences in the relative and absolute amounts of two types of melanin: brown/black eumelanin and red/yellow pheomelanin. Although the majority of research into pigment variation has been done using mammalian models, limited comparative studies support the hypothesis that genes encoding melanogenic enzymes, and their associated biochemical activities, are conserved across vertebrate taxa. However, these studies also suggest that in some cases, the upstream transcriptional regulators of those genes may have diverged in function since vertebrates last shared a common ancestor. To better understand the balance between flexibility and constraint during the evolution of pigment variation among vertebrates, it is critical to better understand the basis of pigment variation in non- mammalian vertebrates as well. Domestic pigeons provide a tremendous opportunity to investigate the genetic and developmental underpinnings of pigment variation due to the large diversity of feather colors and color patterns among individuals. One particularly interesting phenotype known as ?recessive red? is caused by a regulatory mutation reducing expression of Sox10, encoding a transcription factor. This mutation causes cells to produce pheomelanin instead of eumelanin. Interestingly, similar mutations in mouse cause the loss of pigment- producing cells, not just a shift in pigment type, suggesting that the function of Sox10 has diverged among vertebrates. The proposed research seeks to understand Sox10 function during pigment production in birds, and compare it to its proposed function in mammals, with three aims. First, transcriptomic comparisons will be performed between regenerating feathers from wild-type and recessive red pigeons, to identify genes differentially expressed due to the loss of Sox10. Second, several approaches will be used to identify potential binding sites of SOX10 in the pigeon genome, to determine which genes are directly regulated by SOX10. Third, a reverse genetic approach will be taken to mutate these genes in pigeon melanocytes, and thereby elucidate their functions in melanin synthesis. All of these studies will be compared to similar studies in mouse, to understand how similar or different Sox10 function is between these two species. This work will pioneer the use of domestic pigeon as a model to study gene regulation during melanin synthesis, and will generate insights into the basis of skin pigmentation and disease in humans. This research also provides ample opportunities for undergraduate research projects, fostering the development of students? scientific and technical skillsets.
