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 language | English (US) |
|---|---|
| Pages (from-to) | 1802-1820 |
| Number of pages | 19 |
| Journal | Journal of Neuroscience |
| Volume | 38 |
| Issue number | 7 |
| DOIs | |
| State | Published - Feb 14 2018 |
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Keywords
- Myelination and remyelination
- Oligodendrocyte differentiation
- Oligodendrocyte regeneration
- Oligodendroglial lineage progression
- Oligodendroglial progenitor cells
- Sox2
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Sox2 is essential for oligodendroglial proliferation and differentiation during postnatal brain myelination and CNS remyelination. / Zhang, Sheng; Zhu, Xiaoqing; Gui, Xuehong; Croteau, Christopher; Song, Lanying; Xu, Jie; Wang, Aijun; Bannerman, Peter; Guo, Fuzheng.
In: Journal of Neuroscience, Vol. 38, No. 7, 14.02.2018, p. 1802-1820.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Sox2 is essential for oligodendroglial proliferation and differentiation during postnatal brain myelination and CNS remyelination
AU - Zhang, Sheng
AU - Zhu, Xiaoqing
AU - Gui, Xuehong
AU - Croteau, Christopher
AU - Song, Lanying
AU - Xu, Jie
AU - Wang, Aijun
AU - Bannerman, Peter
AU - Guo, Fuzheng
PY - 2018/2/14
Y1 - 2018/2/14
N2 - 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.
AB - 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.
KW - Myelination and remyelination
KW - Oligodendrocyte differentiation
KW - Oligodendrocyte regeneration
KW - Oligodendroglial lineage progression
KW - Oligodendroglial progenitor cells
KW - Sox2
UR - http://www.scopus.com/inward/record.url?scp=85042134292&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042134292&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.1291-17.2018
DO - 10.1523/JNEUROSCI.1291-17.2018
M3 - Article
VL - 38
SP - 1802
EP - 1820
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 7
ER -