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

Magnus, Tim, Coksaygan, Turhan, Korn, Thomas, Xue, Haipeng, Arumugam, Thiruma V., Mughal, Mohamed R., Eckley, D. Mark, Tang, Sung-Chun, DeTolla, Louis, Rao, Mahendra S., Cassiani-Ingoni, Riccardo and Mattson, Mark P. (2007) Evidence that nucleocytoplasmic Olig2 translocation mediates brain-injury-induced differentiation of glial precursors to astrocytes. Journal of Neuroscience Research, 85 10: 2126-2137. doi:10.1002/jnr.21368


Author Magnus, Tim
Coksaygan, Turhan
Korn, Thomas
Xue, Haipeng
Arumugam, Thiruma V.
Mughal, Mohamed R.
Eckley, D. Mark
Tang, Sung-Chun
DeTolla, Louis
Rao, Mahendra S.
Cassiani-Ingoni, Riccardo
Mattson, Mark P.
Title Evidence that nucleocytoplasmic Olig2 translocation mediates brain-injury-induced differentiation of glial precursors to astrocytes
Journal name Journal of Neuroscience Research   Check publisher's open access policy
ISSN 0360-4012
1097-4547
Publication date 2007-08-01
Sub-type Article (original research)
DOI 10.1002/jnr.21368
Volume 85
Issue 10
Start page 2126
End page 2137
Total pages 12
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Language eng
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.
Keyword glial progenitors
Olig2
astrocytes
NG2
stabwound
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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Created: Tue, 17 Nov 2009, 22:21:57 EST