Regulation of myelin development.

Abstract

During the final stage of oligodendrocyte differentiation, oligodendrocyte precursors cease proliferating, and coordinately activate the set of genes encoding the myelin-specific structural proteins. Two homeodomain-containing transcription factors, SCIP and Gtx, by virtue of their temporal patterns of expression, are implicated in the regulation of this process. SCIP is expressed in dividing oligodendrocyte precursors, and its expression is downregulated prior to the onset of oligodendrocyte differentiation. Gtx, in contrast, is expressed in post-mitotic, differentiated oligodendrocytes, and its expression parallels that of the myelin-specific mRNA in a variety of physiologically relevant circumstances. In addition, Gtx binds to several sites within the MBP, PLP and Gtx promoters in a sequence-specific manner probably by way of the core homeodomain binding motif. A third transcription factor, NFI, is also important for oligodendrocyte-specific gene expression, since it turns off myelin gene expression in non-myelinating cells. These three transcription factors are thus important for the normal process of oligodendrocyte differentiation and myelination, and may be involved in the molecular pathogenesis of both demyelination and remyelination in multiple sclerosis.