| During vertebrate embryonic development, neural crest cells normally segregate from the dorsal neural tube and disperse to produce both neuronal and non-neuronal derivatives in specific embryonic locations. Previous studies have demonstrated that cultured crest cell populations that do not disperse irreversibly lose the ability to produce neurons, but retain the ability to produce non-neuronal derivatives.;I have now shown that preventing crest cell dispersal leads to cell-contact mediated cell death, correlated with the loss of neurogenic ability. Blocking cell death with a caspase inhibitor, zVAD-fmk, rescues neurogenic ability, suggesting that a neurogenic precursor population is specifically lost.;Evidence from studies of development in the frog Xenopus laevis suggested that cell-cell signaling involving the vertebrate Notch and Delta genes affect the development of neural crest cell populations. I therefore decided to test the role of Notch-Delta signaling among nascent crest cells, by co-culturing nascent crest cells with Delta expressing cells at different times during their development. Contact with Delta expressing cells initially leads to increased cell death as well as a subsequent decrease in neurogenesis. This decrease in neurogenesis is also due to the death of a neurogenic subpopulation, as it is mitigated by blocking the onset of cell death with caspase inhibitors. Therefore, signaling mediated by the Delta ligand is functionally similar to the contact-mediated signaling that leads to the loss of neurogenic potential in crest populations cultured at high cell density.;The loss of neurogenic potential that occurs either as a result of preventing dispersal or via Delta-mediated signaling only occurs within nascent crest cell populations; crest cell populations that disperse immediately do not exhibit E either cell death or decreased neurogenesis in response to either contact or Delta signaling. However, Delta signaling leads to a specific decrease in melanogenesis within older, dispersed crest cell populations. Together, these results suggest a role for cell-cell contact, mediated by the Notch and Delta genes, in at least two temporally and spatially distinct fate-specification events that function to orchestrate the process of phenotypic diversification within neural crest cell.;This dissertation contains material published as abstracts as well as co-authored manuscripts. |
