Molecular studies on oligodendrocyte and interneuron development in the vertebrate central nervous system

The vertebrate central nervous system (CNS) is a very complex and highly organized system that is comprised of two different cell types, neurons and glia. Neurons are primarily responsible for information processing, whereas glial cells are the supportive elements in the nervous system. There are three major subtypes of glial cells: oligodendrocytes, astrocytes and microglia. Although neurons and glia play important roles in CNS, the mechanisms regulating their development remain unclear. In this study, I focus the function of several transcription factors in the development of oligodendrocytes and interneurons.; In the developing spinal cord, O1ig2, Olig1, Sox10 and Nkx2.2 play essential roles in oligodendrocyte specification and differentiation. My results suggest that overexpression of Olig2, Olig1 or Sox10 alone is sufficient to induce precocious oligodendrocyte differentiation in embryonic chicken spinal cord. In addition, I presented evidence that reduced gene dosage in Olig2, Sox10, Nkx2.2 and Olig1 heterozygous embryos resulted in a delayed oligodendrocyte differentiation and maturation. Thus, the control of oligodendrocyte differentiation by these transcription factors appears to be exquisitely sensitive to gene dosage and is affected by both haploinsufficiency and over-dosage.; I also studied the involvement of two transcription factors in the development of interneurons. Olig3 was identified as the third member of the Olig family including Olig1 and Olig2. BrdU labeling demonstrated that ventral Olig3 was expressed in the postmitotic neurons, whereas dorsal Olig3 was expressed in the dividing neural progenitor cells. Loss of function and gain-of function studies suggest that Olig3 is a downstream gene of Nkx2.2 in V3 interneurons and its function in the development of V3 neurons remains to be characterized.; AP-2alpha is the first identified member of the AP-2 family with a predominant expression in neural crest cells, but its expression and function in the development of the CNS has not been well characterized. The expression studies revealed that AP-2alpha was expressed in specific domains in the diencephalons, midbrain, hindbrain and spinal cord where it was found to be expressed in the differentiating field. However, gain-of-function and loss-of-function assays indicated that AP-2alpha did not affect the development of neurons in spinal cord.