Sox2 Is Essential for Oligodendroglial Proliferation and Differentiation during Postnatal Brain Myelination and CNS Remyelination

The Journal of Neuroscience, 2018 · DOI: 10.1523/JNEUROSCI.1291-17.2018 · Published: February 14, 2018

Simple Explanation

Myelin formation and repair in the central nervous system (CNS) relies on the development of oligodendrocytes, cells that produce myelin. This study investigates the role of Sox2, a protein involved in stem cell regulation, in oligodendrocyte development in the brain. The study found that Sox2 is crucial for both the proliferation of oligodendrocyte precursor cells (OPCs) and their subsequent differentiation into mature oligodendrocytes in the brain. Mice lacking Sox2 in oligodendrocytes showed impaired motor function and deficits in brain myelination. The research also indicated that Sox2 is necessary for the regeneration of oligodendrocytes during remyelination, the process of repairing damaged myelin, in both the brain and spinal cord. This suggests that targeting Sox2 could be a potential therapeutic strategy for promoting myelin repair in neurological disorders.

Study Duration

Not specified

Participants

Transgenic mice (C57BL/6 background), both male and female

Evidence Level

Not specified

Key Findings

1
Sox2 is expressed in OPCs in the postnatal and adult CNS, and transiently upregulated in newly differentiated OLs during developmental myelination and in newly regenerated OLs during remyelination.
2
Sox2 is essential for brain developmental myelination by regulating OPC proliferation and OL differentiation.
3
Sox2 is required for OPC proliferation and/or OL regeneration not only in autoimmune-induced spinal cord demyelination lesions but also in chemical-induced brain demyelination lesions.

Research Summary

This study investigates the role of Sox2 in oligodendrocyte development and myelination in the brain and spinal cord. The researchers used genetic approaches in mice to disrupt Sox2 function in oligodendroglial lineage cells at different developmental stages. The findings demonstrate that Sox2 is essential for OPC proliferation and OL differentiation during postnatal brain development and is also required for myelin repair in both the demyelinated spinal cord and brain. The study suggests that Sox2 may be a therapeutic target for promoting OL regeneration and CNS remyelination, with potential implications for treating myelin-related neurological disorders.

Practical Implications

Therapeutic Target

Sox2 may be a potential therapeutic target for promoting myelin repair in neurological disorders.

CNS Myelin Formation and Repair

Sox2 regulates CNS myelin formation and repair in CNS region and context-dependent manners.

Remyelination

Sox2 is required for myelin repair by regulating OPC proliferation and/or OL differentiation in both the demyelinated spinal cord and brain.

Study Limitations

1
The mechanisms underlying the CNS region-dependent role of Sox2 are unclear.
2
The remyelination study did not provide definitive evidence that Sox2 is required for remyelination by directly regulating OL differentiation.
3
Whether Sox2 expression through genetic and/or viral-mediated approaches is sufficient to promote endogenous CNS remyelination after myelin damage needs further investigation.

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