Abstract
In the developing vertebrate nervous system, multipotent neural stem cells produce both neurons and glia. OLIG2 is a basic helix–loop–helix transcription factor that plays critical roles in oligodendrocyte and motor neuron development; however, its role in astrocytic development remains elusive. In this study, we analyzed an effect of OLIG2 on cytokine-induced astrocytic differentiation from mouse telencephalic neuroepithelial cells. We show that the presence of OLIG2 protein leads to inhibition of the promoter activation of astrocyte-specific glial fibrillary acidic protein gene. We found that OLIG2 abolishes complex formation between a transcriptional coactivator p300 and a transcription factor, signal transducer and activator of transcription 3 (STAT3), which is activated by astrocytic differentiation-inducing cytokines, such as leukemia inhibitory factor (LIF). The enforced expression of OLIG2 in neuroepithelial cells inhibits the LIF-induced astrocytic differentiation. We also show that the OLIG2 protein in the nuclei of neural precursor cells disappears in accordance with astrocytic differentiation during culture with LIF. Together, these results reveal a novel molecular function of OLIG2 on the astrocyte development.
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Abbreviations
- STAT3:
-
signal transducer and activator of transcription 3
- LIF:
-
leukemia inhibitory factor
- GFAP:
-
glial fibrillary acidic protein
- bHLH:
-
basic helix–loop–helix
- GFP:
-
green fluorescent protein
- bFGF:
-
basic fibroblast growth factor
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Acknowledgements
We thank Dr. K Ikenaka for helpful discussion and Dr. M Raff for critical reading of the manuscript. We also thank Dr. T Kitamura for Plat-E cells, and members of our laboratory for valuable discussions and technical advice. We are very grateful to Ms. Y Noguchi for her secretarial assistance, and also thank Ms. K Kaneko and Ms. Y Saiki for technical help. This work was supported in part by grant-in-aid for 21st Century COE Research from Ministry of Education, Science and Culture ‘Cell Fate Regulation Research and Education Unit’; Scientific Research (B); Specially Promoted Research from the Ministry of Education, Culture, Science, Sports and Technology; Nakajima Foundation; Uehara Memorial Foundation; Japan Brain Foundation; Higo Foundation; Human Frontier Science Program; and the Virtual Research Institute of Aging of Nippon Boehringer Ingelheim.
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Fukuda, S., Kondo, T., Takebayashi, H. et al. Negative regulatory effect of an oligodendrocytic bHLH factor OLIG2 on the astrocytic differentiation pathway. Cell Death Differ 11, 196–202 (2004). https://doi.org/10.1038/sj.cdd.4401332
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DOI: https://doi.org/10.1038/sj.cdd.4401332
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