Unfolded protein response, activated by OASIS family transcription factors, promotes astrocyte differentiation

Atsushi Saito, Soshi Kanemoto, Noritaka Kawasaki, Rie Asada, Hideo Iwamoto, Mami Oki, Hidetaka Miyagi, Soutarou Izumi, Tsukasa Sanosaka, Kinichi Nakashima and Kazunori Imaizumi ()
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Atsushi Saito: Institute of Biomedical & Health Sciences, University of Hiroshima
Soshi Kanemoto: Institute of Biomedical & Health Sciences, University of Hiroshima
Noritaka Kawasaki: Institute of Biomedical & Health Sciences, University of Hiroshima
Rie Asada: Institute of Biomedical & Health Sciences, University of Hiroshima
Hideo Iwamoto: Institute of Biomedical & Health Sciences, University of Hiroshima
Mami Oki: Institute of Biomedical & Health Sciences, University of Hiroshima
Hidetaka Miyagi: Institute of Biomedical & Health Sciences, University of Hiroshima
Soutarou Izumi: Institute of Biomedical & Health Sciences, University of Hiroshima
Tsukasa Sanosaka: Laboratory of Molecular Neuroscience, Graduate School of Biological Sciences, Nara Institute of Science and Technology
Kinichi Nakashima: Laboratory of Molecular Neuroscience, Graduate School of Biological Sciences, Nara Institute of Science and Technology
Kazunori Imaizumi: Institute of Biomedical & Health Sciences, University of Hiroshima

Nature Communications, 2012, vol. 3, issue 1, 1-13

Abstract: Abstract OASIS is a member of the CREB/ATF family of transcription factors and modulates cell- or tissue-specific unfolded protein response signalling. Here we show that this modulation has a critical role in the differentiation of neural precursor cells into astrocytes. Cerebral cortices of mice specifically deficient in OASIS (Oasis−/−) contain fewer astrocytes and more neural precursor cells than those of wild-type mice during embryonic development. Furthermore, astrocyte differentiation is delayed in primary cultured Oasis−/− neural precursor cells. The transcription factor Gcm1, which is necessary for astrocyte differentiation in Drosophila, is revealed to be a target of OASIS. Introduction of Gcm1 into Oasis−/− neural precursor cells improves the delayed differentiation of neural precursor cells into astrocytes by accelerating demethylation of the Gfap promoter. Gcm1 expression is temporally controlled by the unfolded protein response through interactions between OASIS family members during astrocyte differentiation. Taken together, our findings demonstrate a novel mechanism by which OASIS and its associated family members are modulated by the unfolded protein response to finely control astrocyte differentiation.

Date: 2012
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DOI: 10.1038/ncomms1971

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