Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, China 200092;
Department of Psychiatry and Behavioral Sciences, Intellectual Development and Disabilities Research Center, University of California, Los Angeles, CA 90095.
Proc Natl Acad Sci U S A. 2017 Aug 22;114(34):9188-9193. doi: 10.1073/pnas.1706069114. Epub 2017 Aug 8.
The prenatal period of cortical development is important for the establishment of neural circuitry and functional connectivity of the brain; however, the molecular mechanisms underlying this process remain unclear. Here we report that disruption of the actin-cytoskeletal network in the developing mouse prefrontal cortex alters dendritic morphogenesis and synapse formation, leading to enhanced formation of fear-related memory in adulthood. These effects are mediated by a brain-enriched microRNA, miR-9, through its negative regulation of diaphanous homologous protein 1 (Diap1), a key organizer of the actin cytoskeletal assembly. Our findings not only revealed important regulation of dendritogenesis and synaptogenesis during early brain development but also demonstrated a tight link between these early developmental events and cognitive functions later in life.
皮质发育的产前阶段对于大脑神经回路的建立和功能连接非常重要；然而，这一过程的分子机制尚不清楚。在这里，我们报告说，在发育中的小鼠前额叶皮层中破坏肌动蛋白细胞骨架网络会改变树突形态发生和突触形成，导致成年后与恐惧相关的记忆形成增强。这些影响是由一种富含大脑的 microRNA，miR-9 通过其对肌动蛋白细胞骨架组装的关键调节蛋白 diaphanous 同源蛋白 1（Diap1）的负调控介导的。我们的研究结果不仅揭示了早期大脑发育过程中树突发生和突触形成的重要调节作用，还表明这些早期发育事件与生命后期的认知功能之间存在紧密联系。
