According to a study published in Science, OLIG1, a basic helix–loop–helix transcription factor, is needed for the repair of demyelinating lesions that occur in multiple sclerosis. OLIG2 is already known to be required for the specification of oligodendrocytes and motor neurons during vertebrate embryogenesis. OLIG1 is coexpressed with OLIG2 in oligodendrocytes during development but, until now, its functions have remained a mystery.

Multiple sclerosis is caused by the death of mature oligodendrocytes, which leads to the loss of myelin sheaths. Fluctuating symptoms are a hallmark of this condition, and result from episodes of demyelination followed by the generation of new oligodendrocytes and remyelination. However, remyelination does not always occur, leading to the progressive deterioration that is characteristic of multiple sclerosis. Arnett and co-workers now show that the mechanisms that lead to remyelination in the adult brain parallel those that occur during the development of oligodendrocytes.

The authors first investigated the distribution of OLIG proteins during development. Both OLIG1 and OLIG2 were found in the nuclei of oligodendrocytes and oligodendrocyte progenitor cells throughout the CNS of neonatal mice. However, whereas OLIG2 continued to be expressed in nuclei throughout development, OLIG1 was found mainly in the cytoplasm at 2 weeks after birth, and only in the cytoplasm of white matter in adult animals.

The next step was to investigate the distribution of OLIG proteins after demyelination. As in development, OLIG1 was found in the nuclei of cells within toxicity-induced demyelinating lesions in mice. Similarly, studies of post-mortem tissue from six patients with multiple sclerosis showed evidence for OLIG1 in the nuclei of oligodendrocytes in the white matter at the edges of active and chronic lesions, but in the cytoplasm of cells in normal white matter.

As remyelination is most likely to occur in active lesions, these data indicate that the relocation of OLIG1 to nuclei might be important for repair after white matter injury. This was confirmed by studies of mice that lacked OLIG1: a fully myelinated brain and spinal cord developed normally but there was little remyelination after toxicity-induced demyelination. Specifically, oligodendrocyte progenitor cells did not differentiate in these animals, underscoring a role for OLIG1 in differentiation of these cells and subsequent remyelination.

Therefore, intracellular localization of OLIG1 changes over the course of oligodendrocyte development, having a subtle effect during early development and a marked effect during remyelination. The parallels between the mechanisms involved in development and remyelination might help to identify a new therapeutic approach for multiple sclerosis.