| Description |
Glial cells are the most numerous cells of the central nervous system (CNS) and play various important roles in regulating appropriate neuronal function. Glial cells and neurons arise from common multipotent progenitors, and understanding their lineage relationships and fate determination is an important challenge in developmental biology. This dissertation addresses several aspects of the biology of spinal cord gliogenesis. First, methods were described for isolation of purified neural precursor cells, including glial restricted precursor (GRP) cells, from the embryonic spinal cord. Second, an immortalized GRP cell line was created by infecting purified GRP cells with regulatable v-myc retroviruses. This immortalized cell line, like normal GRP cells, can differentiate into oligodendrocytes and astrocytes with appropriate signals. This GRP cell line will provide a large population of homogeneous cells for the study of molecular mechanisms underlying glial differentiation and for clinical applications such as drug screening and optimization of transplantation protocol. Third, to extend our understanding of glial lineage relationships in the context of normal embryogenesis, the spatiotemporal expression patterns of several glial markers were examined using in situ hybridization and immunohistochemistry. Finally, to determine how different glial fates are determined from GRP cells, the transcription factors Hes1 and Hes5 were overexpressed in cultured GRP cells by retroviral infection and the fate of infected cells was analyzed. The results show that Hes1, but not Hes5, plays an important role in regulating the astrocyte versus oligodendrocyte fate choice in GRP cells. Taken together, these results provide novel insights into the process of glial differentiation and make available tools to further dissect the process of gliogenesis. |
