| Description |
Cell lineage and acquisition of cell type specific properties in the spinal cord, and subsequent differentiation of neurons are processes critical to the development of the embryo, but are still not well understood. Using a combination of cell culture techniques, molecular biology, electrophysiology, and calcium imaging, we have identified and characterized cell lineage in the spinal cord by elucidating the developmental potential, gene expression profiles, growth factor, and other culture condition requirements of a central nervous system (CNS) stem cell and its neuronal progeny. In this dissertation, I present evidence that the neuroepithelial (NEP) cell is a multipotent CNS stem cell which will self-renew in the presence of fibroblast growth factor (FGF), and has the potential to generate all major phenotypes of the mature CNS. This NEP cell FGF requirement is due to the expression of critical FGF receptors and the lack of expression of other growth factor receptors, providing a molecular basis for its FGF dependence. The NEP cell generates CNS derivatives via the generation of intermediate lineage restricted precursors that differ from each other and from NEP cells. Neuronal restricted precursors (NRPs) were identified and characterized. Differentiation is influenced by extrinsic environmental signals that are stage and cell type specific. These results represent an important step toward the understanding of the differentiation process in particular and spinal cord development in general, and will ultimately aid in endeavors for gene discovery, drug screening, and therapeutic applications. |
