Sox2 Sustains Recruitment of Oligodendrocyte Progenitor Cells following CNS Demyelination and Primes Them for Differentiation during Remyelination

Chao Zhao, Dan Ma, Malgorzata Zawadzka, Stephen P. J. Fancy, Lowri Elis-williams, Guy Bouvier, John H. Stockley, Glaucia Monteiro De Castro, Bowei Wang, Sabrina Jacobs, Patrizia Casaccia, Robin J. M. Franklin

Research output: Contribution to journalArticlepeer-review

Abstract

The Sox family of transcription factors have been widely studied in the context of oligodendrocyte development. However, comparatively little is known about the role of Sox2, especially during CNS remyelination. Here we show that the expression of Sox2 occurs in oligodendrocyte progenitor cells (OPCs) in rodent models during myelination and in activated adult OPCs responding to demyelination, and is also detected in multiple sclerosis lesions. In normal adult white matter of both mice and rats, it is neither expressed by adult OPCs nor by oligodendrocytes (although it is expressed by a subpopulation of adult astrocytes). Overexpression of Sox2 in rat OPCs in vitro maintains the cells in a proliferative state and inhibits differentiation, while Sox2 knockout results in decreased OPC proliferation and survival, suggesting that Sox2 contributes to the expansion of OPCs during the recruitment phase of remyelination. Loss of function in cultured mouse OPCs also results in an impaired ability to undergo normal differentiation in response to differentiation signals, suggesting that Sox2 expression in activated OPCs also primes these cells to eventually undergo differentiation. In vivo studies on remyelination following experimental toxin-induced demyelination in mice with inducible loss of Sox2 revealed impaired remyelination, which was largely due to a profound attenuation of OPC recruitment and likely also due to impaired differentiation. Our results reveal a key role of Sox2 expression in OPCs responding to demyelination, enabling them to effectively contribute to remyelination.
Original languageEnglish
Pages (from-to)11482-11499
JournalJournal of Neuroscience
Volume35
Issue number33
DOIs
Publication statusPublished - 19 Aug 2015

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Copyright©2015 the authors. Articles are released under a Creative Commons Attribution License after a 6 months embargo

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