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Per3 基因,生物钟基因,在小鼠大脑皮层胚胎发育中的作用。

Role of Per3, a circadian clock gene, in embryonic development of mouse cerebral cortex.

机构信息

Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Japan.

Department of Pediatrics, Jichi medical university, Tochigi, Japan.

出版信息

Sci Rep. 2019 Apr 10;9(1):5874. doi: 10.1038/s41598-019-42390-9.

Abstract

Per3 is one of the primary components of circadian clock system. While circadian dysregulation is known to be involved in the pathogenesis of several neuropsychiatric diseases. It remains largely unknown whether they participate in embryonic brain development. Here, we examined the role of clock gene Per3 in the development of mouse cerebral cortex. In situ hybridization analysis revealed that Per3 is expressed in the developing mouse cortex. Acute knockdown of Per3 with in utero electroporation caused abnormal positioning of cortical neurons, which was rescued by RNAi-resistant Per3. Per3-deficient cells showed abnormal migration phenotypes, impaired axon extension and dendritic arbor formation. Taken together, Per3 was found to play a pivotal role in corticogenesis via regulation of excitatory neuron migration and synaptic network formation.

摘要

Per3 是昼夜节律钟系统的主要组成部分之一。虽然昼夜节律失调被认为参与了几种神经精神疾病的发病机制,但它们是否参与胚胎大脑发育在很大程度上尚不清楚。在这里,我们研究了时钟基因 Per3 在小鼠大脑皮层发育中的作用。原位杂交分析显示 Per3 在发育中的小鼠皮层中表达。通过宫内电穿孔进行 Per3 的急性敲低导致皮质神经元的异常定位,而 RNAi 抗性 Per3 可挽救这种异常定位。Per3 缺陷细胞表现出异常的迁移表型,轴突延伸和树突分支形成受损。总之,Per3 通过调节兴奋性神经元迁移和突触网络形成,在皮质发生中发挥关键作用。

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