Department of Biochemistry, Institute of Biomedical & Health Sciences, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Nat Commun. 2012 Jul 24;3:967. doi: 10.1038/ncomms1971.
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.
OASIS 是 CREB/ATF 转录因子家族的成员，可调节细胞或组织特异性未折叠蛋白反应信号。在这里，我们表明这种调节在神经前体细胞分化为星形胶质细胞中起着关键作用。在胚胎发育过程中，特异性缺乏 OASIS（Oasis(-/-)）的小鼠大脑皮质中星形胶质细胞比野生型小鼠少，神经前体细胞多。此外，Oasis(-/-)原代培养神经前体细胞中的星形胶质细胞分化延迟。在果蝇中，星形胶质细胞分化所必需的转录因子 Gcm1 被揭示为 OASIS 的靶标。将 Gcm1 导入 Oasis(-/-)神经前体细胞可通过加速 Gfap 启动子的去甲基化来改善神经前体细胞向星形胶质细胞的分化延迟。Gcm1 的表达受未折叠蛋白反应的时空控制，通过星形胶质细胞分化过程中 OASIS 家族成员之间的相互作用。总之，我们的研究结果表明了一种新的机制，即未折叠蛋白反应通过调节 OASIS 及其相关家族成员来精细控制星形胶质细胞分化。
