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 of myelin-forming glial cells. Previous experiments in cloning and characterizing individual transcription factors (e.g. MYT1, MYT1-L, rKr2) and components of the signal transduction pathways (e.g. PTPepsilon) expressed by oligodendrocytes have expanded to a more global effort. Employing microarray technology, we have identified sets of transcription factors and cell surface receptors that are expressed by oligodendrocytes at distinct stages in their development. Members from two families of molecules that mediate cell-cell interactions, the ephrin and neuropilin receptors, were found to be selectively and highly expressed by oligodendrocytes. Ongoing functional studies suggest a possible role for these molecules in the migration of oligodendrocyte progenitors and in the establishment of neuronal-glial contacts. Our CNP-geo transgenic mice, in which oligodendrocytes are specifically tagged with a lacZ-antibiotic resistance reporter, have been used as transplantation donors to determine whether bone marrow stem cell populations are capable of migrating into the nervous system and differentiating into myelin-forming glial cells and whether the geo-tagged cells can promote recovery when introduced into jimpymsd mice that lack mature oligodendrocytes. These studies form the basis for devising strategies to promote remyelination in diseases such as multiple sclerosis, Pelizaeus-Merzbacher disease and spinal cord injury, either by directly supplying normal progenitors or by stimulating endogenous oligodendrocyte progenitors to proliferate, migrate and differentiate.
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