The program of gene expression in a cell is controlled by a selected array of transcription factors that are activated in response to extracellular cues. The focus of this section is on the discovery and functional analysis of the network of genes involved in the development and operation of the nervous system. The differentiation of neural stem cells to oligodendrocytes or neurons requires distinct sets of transcription factors, and we have cloned several such factors. MYT1 (Myelin transcription Factor 1), a novel member of the zinc finger superfamily, may be instrumental in early stages of oligodendrocyte development and myelin production as well as during regeneration, in each case by coordinating the expression of myelin genes. Another member of the MYT1 family (named MYT1L) is not expressed in oligodendrocytes, but instead marks neurons at the time they are undergoing their terminal mitosis. The MYT1 and MYT1L proteins are strikingly upregulated following spinal cord injury, suggesting that both neuronal and glial progenitor cells may have been stimulated to divide or were recruited to the site of injury. Another zinc finger named rKr2 is selectively expressed in granule cell neurons and oligodendrocyte progenitors. The developmental expression and localization of these multifingered zinc proteins suggests that each may play a role in the differentiation of neurons and oligodendrocytes in the mammalian central nervous system. The individual functions of these transcription factors are being examined in knockout and dominant negative transgenic mice and in molecular interaction assays. To identify the entire set of transcription factors that are expressed by progenitors and oligodendrocytes in response to the signalling molecules known to affect the differentiation or survival of oligodendrocytes, we have employed a microarray analysis combined with a transgenic mouse strategy for isolating pure populations of myelin forming cells. The transgenic mice in which the myelin-forming cells are tagged with a GEO reporter are also being used to pinpoint the origins of Schwann cells and oligodendrocytes in the developing nervous system. These studies form the basis for devising strategies to promote remyelination in diseases such as multiple sclerosis, Pelizaeus- Merzbacher disease and spinal cord injury, by stimulating oligodendrocyte progenitors to proliferate, migrate and differentiate. - Gene regulation, transcription factors, transgenic mice, oligodendrocytes, neurons, muliple sclerosis, regeneration, spinal cord injury, Pelizaeus-Merzbacher Disease
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