DiGeorge syndrome critical region gene 2 (DGCR2), a schizophrenia risk gene, regulates dendritic spine development through cell adhesion.
DiGeorge syndrome critical region gene 2 (DGCR2), a schizophrenia risk gene, regulates dendritic spine development through cell adhesion.
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DOI：
10.1186/s13578-023-01081-9
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发表时间：
2023-07-21
影响因子：
7.5
通讯作者：
Fei, Erkang
中科院分区：
文献类型：
--
作者：
Ren, Dongyan;Luo, Bin;Chen, Peng;Yu, Lulu;Xiong, Mingtao;Fu, Zhiqiang;Zhou, Tian;Chen, Wen-Bing;Fei, Erkang
关键词：
树突棘是锥体神经元上兴奋性突触的部位，其发育对神经回路和脑功能至关重要。脊柱形状、大小或数量的改变与神经系统疾病有关，包括精神分裂症。DiGeorge综合征关键区基因2（DGCR 2）是22q11.2缺失综合征（22 q11 DS）中的一个缺失基因，是精神分裂症的高危基因。精神分裂症患者DGCR 2表达降低。然而，DGCR 2在精神分裂症或22 q11 DS中的病理生理机制仍不清楚。在这里，我们报告DGCR 2表达增加，在神经发育期间，并在突触后密度（PSD）丰富。DGCR 2缺陷的海马神经元形成较少的棘。与此一致，DGCR 2缺陷小鼠海马中的突触能传递和突触可塑性降低。进一步的分子研究表明，DGCR 2的胞外结构域（ECD）负责其与细胞粘附分子Neurexin 1（NRXN 1）的跨细胞相互作用和脊柱发育。因此，在DGCR 2缺陷小鼠中观察到异常行为，如焦虑。这些观察结果表明，DGCR 2是一种新的细胞粘附分子所需的脊柱发育和突触可塑性，其缺陷诱导小鼠的异常行为。本研究为DGCR 2在22 q11 DS及相关精神障碍中的作用提供了潜在的病理生理机制。在线版本包含补充材料，可通过10.1186/s13578-023-01081-9获得。
Dendritic spines are the sites of excitatory synapses on pyramidal neurons, and their development is crucial for neural circuits and brain functions. The spine shape, size, or number alterations are associated with neurological disorders, including schizophrenia. DiGeorge syndrome critical region gene 2 (DGCR2) is one of the deleted genes within the 22q11.2 deletion syndrome (22q11DS), which is a high risk for developing schizophrenia. DGCR2 expression was reduced in schizophrenics. However, the pathophysiological mechanism of DGCR2 in schizophrenia or 22q11DS is still unclear. Here, we report that DGCR2 expression was increased during the neurodevelopmental period and enriched in the postsynaptic densities (PSDs). DGCR2-deficient hippocampal neurons formed fewer spines. In agreement, glutamatergic transmission and synaptic plasticity were decreased in the hippocampus of DGCR2-deficient mice. Further molecular studies showed that the extracellular domain (ECD) of DGCR2 is responsible for its transcellular interaction with cell adhesion molecule Neurexin1 (NRXN1) and spine development. Consequently, abnormal behaviors, like anxiety, were observed in DGCR2-deficient mice. These observations indicate that DGCR2 is a novel cell adhesion molecule required for spine development and synaptic plasticity, and its deficiency induces abnormal behaviors in mice. This study provides a potential pathophysiological mechanism of DGCR2 in 22q11DS and related mental disorders. The online version contains supplementary material available at 10.1186/s13578-023-01081-9.
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DOI：
10.1523/jneurosci.1003-21.2021
发表时间：
2022-01-26
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chen P;Liu Z;Zhang Q;Lin D;Song L;Liu J;Jiao HF;Lai X;Zou S;Wang S;Zhou T;Li BM;Zhu L;Pan BX;Fei E
通讯作者：
Fei E
影响因子：
16.2
作者：
Ko, Jaewon;Fuccillo, Marc V.;Malenka, Robert C.;Suedhof, Thomas C.
通讯作者：
Suedhof, Thomas C.
影响因子：
2
作者：
Bassett, AS;Chow, EWC;Gatzoulis, MA
通讯作者：
Gatzoulis, MA
影响因子：
1.8
作者：
Molinard-Chenu, Aude;Godel, Michel;Rey, Alicia;Musardo, Stefano;Bodogan, Timea;Vutskits, Laszlo;Bellone, Camilla;Dayer, Alexandre
通讯作者：
Dayer, Alexandre
影响因子：
64.8
作者：
Engert, F;Bonhoeffer, T
通讯作者：
Bonhoeffer, T