Genetics and evelopment nderlie both phenotypic diversity and pathologies with a developmental basis. An increasing number of studies, including genome-wide association studies of disease risk, are linking genetic components to adult phenotypes, but the specific cellular events that link underlying genotype to terminal phenotype can be difficult or impossible to study in many vertebrate systems. Experiments in this project will use an experimentally accessible phenotype (adult pigmentation) in a group of tractable vertebrate organisms (zebrafish and related fishes) to test hypotheses about the developmental connection between genotype and an adult phenotype with relevance to public health. These species develop strikingly different adult pigment patterns through changes in a complex, integrated developmental system characterized by extensive interactions between several migratory, neural crest-derived classes of pigment cells. This project will investigate species-differences in the first cell type to develop impact subsequent pattern development. The experiments in the first aim will determine (i) how the first type of pigment cell class to develop inhibits the development of subsequent chromatophores, (ii) how a genetic pathway evolved to drive the temporal sequence of pigment cell differentiation across species, and (iii) the role of a specific regulatory element in modulating gene expression across species. The experiments in the second aim will determine the developmental basis for a unique adult pigment pattern of vertical bars by determining (i) how cell migration has evolved to initiate the new pattern, and if changes in pigment cells or the tissue environment are responsible for the new pattern potentially through candidate genetic pathways resulting in altered cell differentiation. Training during this project will take place in an integrative environment at the intersection of genomics and empirical developmental biology. The experiments performed and the questions addressed during this project will provide meaningful contributions to understanding the post-embryonic developmental connection between specific genetic differences and diverse adult phenotypes in a model vertebrate system.
This project is relevant to public health because it investigates the developmental processes that connect natural genetic variation to drastically different morphologies in adults. Genome-wide association studies can link natural genetic variation to disease, but cannot examine the developmental processes that cause adult- onset diseases, such as melanoma, to manifest. The system in this study, namely the development and migration of pigment cells in juveniles and adults, is highly relevant as improper regulation of these processes is an underlying driver of melanoma, one of the least treatable cancers in humans.
