PhD

dissertationThe vertebrate central nervous system (CNS) comprises of two types of cell: neurons and glia. In the developing vertebrate neural tube, glia consists of astrocytes, olegodendrocytes and radial glia. Gliogenesis, the generation of glia, is a complex biological process that is necessary for proper nervous system function. Among the molecular mechanisms that control gliogenesis are transcription factors. Transcription factors are regulatory proteins that modulate gene expression and are therefore prime candidates to investigate in order to understand glial development. Several studies have suggested that the ventral neural tube maybe the location from which oligodendrocyte precursors (OLPs) arise. Several transcription factors are specifically expressed in the ventral neural tube and may direct glial specification. To investigate whether such transcription factors may be required for the generation of olibodendrocytes and possible glia, mice harboring targeted delection of Nkx2.2 and Neurogenin3 (Ngn3), two transcription facators expressed in the ventral neural tube, were independently obtained and analyzed for a glial phenotype. In both mice, oligodendrogliogenesis was compromised in the knockout animal but preserved in the wild-type control. Furthermore, in transient transfection assays, both transcription factors were capable of driving gene expression from the proteolipid protein (PLP) promoter. However, not all markers of OLP were affected. In a subsequent study, the expression of astroglial markers was examined in the NKx2.2 and Ngn3 knockout animals. In both mice, astroglial markers were affected. In the Ngn3 mouse, there appeared to be less astrocyte marker expression in the knockout while an increase in radial glial marker expression was noted. In the Nkx2.2 mouse, a decrease in the expression of radial glia markers was observed in the knockout animals. In summary, Nkx2.2 and Ngn3 are required for the normal appearance of olgodendrocytes, astrocyetes and radial glia in the developing CNS and olgodendrocytes, astrocytes and radial glia likely share a common lineage