Sox2 is essential for oligodendroglial proliferation and differentiation during postnatal brain myelination and CNS remyelination

Sheng Zhang, Xiaoqing Zhu, Xuehong Gui, Christopher Croteau, Lanying Song, Jie Xu, Aijun Wang, Peter Bannerman, Fuzheng Guo

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

In the CNS, myelination and remyelination depend on the successful progression and maturation of oligodendroglial lineage cells, including proliferation and differentiation of oligodendroglial progenitor cells (OPCs). Previous studies have reported that Sox2 transiently regulates oligodendrocyte (OL) differentiation in the embryonic and perinatal spinal cord and appears dispensable for myelination in the postnatal spinal cord. However, the role of Sox2 in OL development in the brain has yet to be defined. Wenow report that Sox2 is an essential positive regulator of developmental myelination in the postnatal murine brain of both sexes. Stage-specific paradigms of genetic disruption demonstrated that Sox2 regulated brain myelination by coordinating upstream OPC population supply and downstream OL differentiation. Transcriptomic analyses further supported a crucial role of Sox2 in brain developmental myelination. Consistently, oligodendroglial Sox2-deficient mice developed severe tremors and ataxia, typical phenotypes indicative of hypomyelination, and displayed severe impairment of motor function and prominent deficits of brain OL differentiation and myelination persisting into the later CNS developmental stages. We also found that Sox2 was required for efficient OPC proliferation and expansion and OL regeneration during remyelination in the adult brain and spinal cord. Together, our genetic evidence reveals an essential role of Sox2 in brain myelination and CNS remyelination,and suggests that manipulation of Sox2 and/or Sox2-mediated downstream pathways may be therapeutic in promoting CNS myelin repair.

Original languageEnglish (US)
Pages (from-to)1802-1820
Number of pages19
JournalJournal of Neuroscience
Volume38
Issue number7
DOIs
StatePublished - Feb 14 2018

Keywords

  • Myelination and remyelination
  • Oligodendrocyte differentiation
  • Oligodendrocyte regeneration
  • Oligodendroglial lineage progression
  • Oligodendroglial progenitor cells
  • Sox2

ASJC Scopus subject areas

  • Neuroscience(all)

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