Laboratory of Environmental Molecular Physiology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan.
Sci Rep. 2021 Mar 31;11(1):7295. doi: 10.1038/s41598-021-86442-5.
Activating transcription factor 5 (ATF5) is a member of the cAMP response element binding protein (CREB)/ATF family of basic leucine zipper transcription factors. We previously reported that ATF5-deficient (ATF5) mice exhibited behavioural abnormalities, including abnormal social interactions, reduced behavioural flexibility, increased anxiety-like behaviours, and hyperactivity in novel environments. ATF5 mice may therefore be a useful animal model for psychiatric disorders. ATF5 is highly expressed in the ventricular zone and subventricular zone during cortical development, but its physiological role in higher-order brain structures remains unknown. To investigate the cause of abnormal behaviours exhibited by ATF5 mice, we analysed the embryonic cerebral cortex of ATF5 mice. The ATF5 embryonic cerebral cortex was slightly thinner and had reduced numbers of radial glial cells and neural progenitor cells, compared to a wild-type cerebral cortex. ATF5 deficiency also affected the basal processes of radial glial cells, which serve as a scaffold for radial migration during cortical development. Further, the radial migration of cortical upper layer neurons was impaired in ATF5 mice. These results suggest that ATF5 deficiency affects cortical development and radial migration, which may partly contribute to the observed abnormal behaviours.
激活转录因子 5（ATF5）是 cAMP 反应元件结合蛋白（CREB）/ATF 家族碱性亮氨酸拉链转录因子的成员。我们之前的报告显示，ATF5 缺陷（ATF5）小鼠表现出行为异常，包括异常的社交互动、行为灵活性降低、焦虑样行为增加以及在新环境中过度活跃。因此，ATF5 小鼠可能是一种有用的精神疾病动物模型。ATF5 在皮质发育过程中高度表达于脑室区和室下区，但它在高级脑结构中的生理作用尚不清楚。为了研究 ATF5 小鼠表现出异常行为的原因，我们分析了 ATF5 小鼠的胚胎大脑皮质。与野生型大脑皮质相比，ATF5 胚胎大脑皮质略薄，放射状胶质细胞和神经祖细胞数量减少。ATF5 缺乏还影响了放射状胶质细胞的基底过程，该过程在皮质发育过程中作为放射状迁移的支架。此外，ATF5 小鼠的皮质上层神经元的放射状迁移受损。这些结果表明，ATF5 缺乏会影响皮质发育和放射状迁移，这可能部分导致观察到的异常行为。
