While we know a great deal about genetic and cellular mechanisms of early vertebrate development, we know far less about later processes of organogenesis, and the mechanisms that underlie adult form and its maintenance. Elucidating the mechanisms responsible for these later phenotypes and processes will be absolutely essential for a deeper understanding normal development, and will provide insights into many genetic and acquired disease syndromes. In this proposal, we will continue our studies of post-embryonic vertebrate development, focusing on adult derivatives of the neural crest, embryonic precursor cells that generate many cell and tissues types, including pigment cells and much of the peripheral nervous system. Our previous studies suggest that in addition to cell types that differentiate at early stages, latent neural crest-derived precursors are established during early development then recruited later to generate and maintain adult traits. Using zebrafish pigmentation and peripheral nervous system development as a model, we will test roles for neuregulin and Wnt signals in establishing and maintaining latent precursors of neural crest origin. We will further characterize these precursors to identify their locations, molecular phenotypes, and self-renewal capabilities. Then, we will determine how these precursors are recruited specifically into pigment cell lineages and how interactions among these lineages contribute to pigment pattern formation, focusing on roles for kit, fms, and endothelin receptors b1, which we previously identified as underlying mutant phenotypes with severe adult pigment pattern defects. Finally, by analyzing new mutants and determining their genetic bases, we will identify additional genes and pathways required for post-embryonic development of neural crest derivatives. Together these studies will advance our understanding of post- embryonic derivatives of the neural crest, and more generally, how latent precursor populations contribute to the development and maintenance of adult form. ? ?
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