Inhibition of Autism-Related Crm1 Disrupts Mitosis and Induces Apoptosis of the Cortical Neural Progenitors
Inhibition of Autism-Related Crm1 Disrupts Mitosis and Induces Apoptosis of the Cortical Neural Progenitors
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DOI：
10.1093/cercor/bhaa011
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Jie-Guang Chen
中科院分区：
文献类型：
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作者：
Xue Li;Yue Feng;Meifang Yan;Xiaomeng Tu;Bin Xie;Fangfang Ni;Chunsheng Qu;Jie-Guang Chen
De novo microdeletion of chromosome 2p15–16.1 presents clinically recognizable phenotypes that include mental.retardation, autism, and microcephaly. Chromosomal maintenance 1 (CRM1) is a gene commonly missing in patients with.2p15–16.1 microdeletion and one of two genes found in the smallest deletion case. In this study, we investigate the role and.mechanism of Crm1 in the developing mouse brain by inhibiting the protein or knocking down the gene in vivo. Inhibition.of Crm1 reduces the proliferation and increases p53-dependent apoptosis of the cortical neural progenitors, thereby.impeding the growth of embryonic cerebral cortex. Live imaging of mitosis in ex vivo embryonic brain slices reveals that.inhibition of CRM1 arrests the cortical progenitors at metaphase. The arrested cells eventually slip into a pseudo-G1 phase.without chromosome segregation. The mitotic slippage cells are marked by persistent expression of the spindle assembly.checkpoint (SAC), repressing of which rescues the cells from apoptosis. Our study reveals that activating the SAC and.inducing the mitotic slippage may lead to apoptosis of the cortical neural progenitors. The resulting cell death may well.contribute to microcephaly associated with microdeletion of chromosome 2p15–16.1 involving CRM1.
