Epub: Fancy et al. Evidence that nuclear factor IA inhibits repair after white matter injury. Ann Neurol. 2012. doi: 10.1002/ana.23590.
OBJECTIVE: Chronic demyelination can result in axonopathy and is associated with human neurological conditions such as MS in adults. In this disorder, myelin regeneration is inhibited by impaired differentiation of oligodendrocyte progenitors into myelin-producing oligodendrocytes. However, regulatory factors relevant in human myelin disorders and in myelin regeneration remain poorly understood.
Here we have investigated the role of the transcription factor nuclear factor IA (NFIA) in oligodendrocyte progenitor differentiation during developmental and regenerative myelination
METHODS: NFIA expression patterns in MS as well as developmental expression in mice were evaluated. Functional studies during remyelination were performed using a lysolecithin model, coupled with lentiviral misexpression of NFIA. The role of NFIA during oligodendrocyte lineage development was characterized using chick and mouse models and in vitro culture of oligodendrocyte progenitors. Biochemical mechanism of NFIA function was evaluated using chromatin immunoprecipitation and reporter assays.
RESULTS: NFIA is expressed in oligodendrocyte progenitors, but not differentiated oligodendrocytes during mouse embryonic development. Examination of NFIA expression in white matter lesions of human newborns as well as active MS lesions in adults, revealed that it is similarly expressed in oligodendrocyte progenitors and not oligodendrocytes. Functional studies indicate that NFIA is sufficient to suppress oligodendrocyte progenitor differentiation during adult remyelination and embryonic development through direct repression of myelin gene expression.
INTERPRETATION: These studies suggest that NFIA participates in the control of oligodendrocyte progenitor differentiation and may contribute to the inhibition of remyelination in human myelin disorders
Transcription factors are things that control how DNA is transcribed into RNA. This is then translated into the production of amino acids which make up proteins. This study identifies yet another molecule NF1A that is a switch factor to make immature oligodendrocytes mature into cells that can produce myelin.. This could be a new drug target to promote remyelination.