bHLH Transcription Factor Olig1 Is Required to Repair Demyelinated Lesions in the CNS

Abstract

Olig1 and Olig2 are closely related basic helix-loop-helix (bHLH) transcription factors that are expressed in myelinating oligodendrocytes and their progenitor cells in the developing central nervous system (CNS). Olig2 is necessary for the specification of oligodendrocytes, but the biological functions of Olig1 during oligodendrocyte lineage development are poorly understood. We show here that Olig1 function in mice is required not to develop the brain but to repair it. Specifically, we demonstrate a genetic requirement for Olig1 in repairing the types of lesions that occur in patients with multiple sclerosis.

Differential and cooperative actions of Olig1 and Olig2 transcription factors on immature proliferating cells after contusive spinal cord injury

“…We found that Olig1 introduction after traumatic SCI enhanced OL maturation and myelin-related protein production to a modest extent. This finding is in line with a recent report that Olig1 is required for myelin repair in response to demyelinating injuries during adulthood (Arnett et al, 2004). Interestingly, we found that the coexpression of Olig2 with Olig1 robustly increased the extent of both OL maturation and myelin related protein expression.…”

“…It has been shown that Olig1 deletion does not affect the formation or recruitment of OL progenitors during postnatal development or after a demyelinating insult in adults (Arnett et al, 2004;Xin et al, 2005). In contrast, simultaneous introduction of Olig1 and Olig2 substantially increased the proportion of NG2 or PDGFRa positive OPCs.…”

“…Olig1 was required in the remyelination process after demyeliAdditional Supporting Information may be found in the online version of this article. nated lesions in mature CNS (Arnett et al, 2004). More recent studies showed the involvement of Olig2 in the differentiation of neural and/or glial progenitors after injury (Buffo et al, 2005;Chen et al, 2008).…”

“…More recent studies showed the involvement of Olig2 in the differentiation of neural and/or glial progenitors after injury (Buffo et al, 2005;Chen et al, 2008). It appears that Olig1 and Olig2 have distinct biological functions that could be separable from those of each other after injury and during development (Arnett et al, 2004;Buffo et al, 2005;Xin et al, 2005). Here, we introduced olig1 and olig2 genes, separately or in combination, into immature proliferating cells to determine the effects of these transcription factors on GPC proliferation and differentiation following contusive SCI.…”

Cell Therapy for Multiple Sclerosis

“…Olig1 is an important transcription factor in early oligodendrocyte specification and differentiation. Its induction may stimulate remyelination [114]. Analysis of gene expression profiles during development in the normal adult brain and during demyelination identified several novel regulatory pathways of oligodendrocyte differentiation.…”