Research Abstract


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

2012年7月24日 Nature Communications 3 : 967 doi: 10.1038/ncomms1971


齋藤 敦1, 金本 聡自1, 川崎 範隆1, 浅田 梨絵1, 岩本 秀雄1, 沖 真実1, 宮城 秀考1, 泉 聡太郎1, 佐野坂 司2, 中島 欽一2, 今泉 和則1

  1. 広島大学大学院 医歯薬保健学研究院 分子細胞情報学
  2. 奈良先端科学技術大学院大学 バイオサイエンス研究科 分子神経分化制御
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.