Evidence that nucleocytoplasmic Olig2 translocation mediates brain-injury-induced differentiation of glial precursors to astrocytes

Tim Magnus, Turhan Coksaygan, Thomas Korn, Haipeng Xue, Thiruma V. Arumugam, Mohamed R. Mughal, D. Mark Eckley, Sung Chun Tang, Louis DeTolla, Mahendra S. Rao, Riccardo Cassiani-Ingoni, Mark P. Mattson

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

74 Zitate (Scopus)

Abstract

The mechanisms by which neural and glial progenitor cells in the adult brain respond to tissue injury are unknown. We studied the responses of these cells to stab wound injury in rats and in two transgenic mouse models in which Y/GFP is driven either by Sox2 (a neural stem cell marker) or by Tα-1 (which marks newly born neurons). The response of neural progenitors was low in all nonneurogenic regions, and no neurogenesis occurred at the injury site. Glial progenitors expressing Olig2 and NG2 showed the greatest response. The appearance of these progenitors preceded the appearance of reactive astrocytes. Surprisingly, we found evidence of the translocation of the transcription factor Olig2 into cytoplasm in the first week after injury, a mechanism that is known to mediate the differentiation of astrocytes during brain development. Translocation of Olig2, down-regulation of NG2, and increased glial fibrillary acidic protein expression were recapitulated in vitro after exposure of glial progenitors to serum components or bone morphogentic protein by up-regulation of Notch-1. The glial differentiation and Olig2 translocation could be blocked by inhibition of Notch-1 with the γ-secretase inhibitor DAPT. Together, these data indicate that the prompt maturation of numerous Olig2+ glial progenitors to astrocytes underlies the repair process after a traumatic injury. In contrast, neural stem cells and neuronal progenitor cells appear to play only a minor role in the injured adult CNS.

OriginalspracheEnglisch
Seiten (von - bis)2126-2137
Seitenumfang12
FachzeitschriftJournal of Neuroscience Research
Jahrgang85
Ausgabenummer10
DOIs
PublikationsstatusVeröffentlicht - 1 Aug. 2007
Extern publiziertJa

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