Intrinsic regulators of OPC activation during CNS remyelination-role of Sox2

Understanding the mechanisms of CNS remyelination is central to developing effective means by which this process can be therapeutically enhanced in chronic demyelinating disease such as multiple sclerosis. Progression of oligodendrocyte progenitor cells (OPCs) to mature oligodendrocytes in response to signals in injury environment holds the key for successful myelin regeneration. Here we discuss the role of Sox2, a transcription factor widely implicated in stem cell biology, in CNS myelination and remyelination. We show that Sox2 is expressed in most OPCs at active period of developmental CNS myelination at early postnatal stage but diminished in adults in oligodendrocyte lineage cells. When demyelinating injury occurs the expression of Sox2 in OPCs is transiently increased but down-regulated upon differentiation. Using genetic fate mapping, gain of function and loss of function experiments, we demonstrated that Sox2 sustains the recruitment of OPCs and its up-regulation is essential for CNS remyelination. These findings suggest that Sox2 and its downstream regulatory factors may play an important role in the activation of OPCs following CNS demyelination and subsequent remyelination.