Cell fate programs in the embryo are increasingly well understood, but little is known about those that mediate post-embryonic development. Nevertheless, such programs are essential to the formation of adult phenotypes. As an animal grows and develops, persisting progenitor cells differentiate to produce new tissues or to contribute to the expansion of patterns initiated in the larval stages. These post-embryonic progenitor populations are not well studied, and a focused examination is critical in our efforts to understand how adult phenotypes arise. The neural crest (NC) is an embryonic population of cells uniquely present in vertebrates that gives rise to a diverse range of cell types. It has proven to be an exceptional model system for investigating cell lineage and the dynamic controls of cell fate. Whereas much is known about the NC and the roles of NC cells in embryogenesis, post-embryonic progenitor cells derived from the NC have been far less studied. Prior work in zebrafish has shown that post-embryonic NC-derived progenitors differentiate into various cell types including pigment cells and glia. Outstanding questions about these cells concern their anatomical niches, their range of fates during development and how these fates are specified, and their normal roles and differentiative potential in adults, particularly in the context of regeneration. To address these issues, I have devised a series of experiments in zebrafish.
In Aim 1, I will investigate the role of NC-derived progenitors (NCPs) in larva-to-juvenile fish, focusing primarily on identifying their anatomical location(s) and fate(s). This work will involve mapping single-cell expression data anatomically to locate presumptive niches of progenitor populations, as well as single-cell fate mapping in vivo.
In Aim 2, I will examine the role of NCPs in maintenance of the adult form and the potential of these cells in the context of regeneration using fate mapping and single-cell transcriptomics. The proposed analyses will expand our knowledge of cell fate programs in post-embryonic NC-derived cells and will support future research in stem cell therapeutics and regenerative medicine.
Neural crest (NC) cells give rise to a remarkable number of cell types contributing to disparate systems including the peripheral nervous system, pigmentation, and the skeleton. Despite great strides in our understanding of embryonic NC cells, very little is known about post-embryonic NC-derived progenitor cells and how they contribute to adult phenotypes. A more comprehensive approach focusing on these progenitors will substantially advance stem cell biology and regenerative medicine, addressing fundamental questions about cell fate, lineage, and potential.