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

Nature Communications Volume 3 Page 967- published_at 2012-07-24
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Title ( eng )
Unfolded protein response, activated by OASIS family transcription factors, promotes astrocyte differentiation
Creator
Kawasaki Noritaka
Iwamoto Hideo
Oki Mami
Sanosaka Tsukasa
Nakashima Kinichi
Source Title
Nature Communications
Volume 3
Start Page 967
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.
Descriptions
This work was partly supported by grants from the Japan Society for the Promotion of Science KAKENHI (#22020030, #22800049), Sumitomo Foundation, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Astellas Foundation for Research on Metabolic Disorders, Takeda Science Foundation, The Pharmacological Research Foundation Tokyo, Daiichi-Sankyo Foundation of Life Science, The Naito Foundation, Senri Life Science Foundation, Hokuto Foundation for Bioscience, and The Japan Prize Foundation.
Language
eng
Resource Type journal article
Publisher
Nature Research
Date of Issued 2012-07-24
Rights
This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
Publish Type Version of Record
Access Rights open access
Source Identifier
[ISSN] 2041-1723
[DOI] 10.1038/ncomms1971
[PMID] 22828627
[DOI] https://doi.org/10.1038/ncomms1971