DiGeorge syndrome critical region gene 2 (DGCR2), a schizophrenia risk gene, regulates dendritic spine development through cell adhesion
Abstract Background 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 syndrom...
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Cell & Bioscience |
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| Online Access: | https://doi.org/10.1186/s13578-023-01081-9 |
| _version_ | 1827894866788483072 |
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| author | Dongyan Ren Bin Luo Peng Chen Lulu Yu Mingtao Xiong Zhiqiang Fu Tian Zhou Wen-Bing Chen Erkang Fei |
| author_facet | Dongyan Ren Bin Luo Peng Chen Lulu Yu Mingtao Xiong Zhiqiang Fu Tian Zhou Wen-Bing Chen Erkang Fei |
| author_sort | Dongyan Ren |
| collection | DOAJ |
| description | Abstract Background 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. Results 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. Conclusions 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. |
| first_indexed | 2024-03-12T22:12:37Z |
| format | Article |
| id | doaj.art-15a02c119e6b4ba6845b2c86bd578156 |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-03-12T22:12:37Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-15a02c119e6b4ba6845b2c86bd5781562023-07-23T11:27:37ZengBMCCell & Bioscience2045-37012023-07-0113111410.1186/s13578-023-01081-9DiGeorge syndrome critical region gene 2 (DGCR2), a schizophrenia risk gene, regulates dendritic spine development through cell adhesionDongyan Ren0Bin Luo1Peng Chen2Lulu Yu3Mingtao Xiong4Zhiqiang Fu5Tian Zhou6Wen-Bing Chen7Erkang Fei8School of Life Sciences, Nanchang UniversityInstitute of Life Science, Nanchang UniversityInstitute of Life Science, Nanchang UniversityInstitute of Life Science, Nanchang UniversityInstitute of Life Science, Nanchang UniversityInstitute of Life Science, Nanchang UniversitySchool of Basic Medical Sciences, Nanchang UniversityInstitute of Life Science, Nanchang UniversitySchool of Life Sciences, Nanchang UniversityAbstract Background 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. Results 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. Conclusions 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.https://doi.org/10.1186/s13578-023-01081-9DiGeorge syndrome critical region gene 2 (DGCR2)22q11.2 deletion syndrome (22q11DS)AnxietyCell adhesionDendritic spine |
| spellingShingle | Dongyan Ren Bin Luo Peng Chen Lulu Yu Mingtao Xiong Zhiqiang Fu Tian Zhou Wen-Bing Chen Erkang Fei DiGeorge syndrome critical region gene 2 (DGCR2), a schizophrenia risk gene, regulates dendritic spine development through cell adhesion Cell & Bioscience DiGeorge syndrome critical region gene 2 (DGCR2) 22q11.2 deletion syndrome (22q11DS) Anxiety Cell adhesion Dendritic spine |
| title | DiGeorge syndrome critical region gene 2 (DGCR2), a schizophrenia risk gene, regulates dendritic spine development through cell adhesion |
| title_full | DiGeorge syndrome critical region gene 2 (DGCR2), a schizophrenia risk gene, regulates dendritic spine development through cell adhesion |
| title_fullStr | DiGeorge syndrome critical region gene 2 (DGCR2), a schizophrenia risk gene, regulates dendritic spine development through cell adhesion |
| title_full_unstemmed | DiGeorge syndrome critical region gene 2 (DGCR2), a schizophrenia risk gene, regulates dendritic spine development through cell adhesion |
| title_short | DiGeorge syndrome critical region gene 2 (DGCR2), a schizophrenia risk gene, regulates dendritic spine development through cell adhesion |
| title_sort | digeorge syndrome critical region gene 2 dgcr2 a schizophrenia risk gene regulates dendritic spine development through cell adhesion |
| topic | DiGeorge syndrome critical region gene 2 (DGCR2) 22q11.2 deletion syndrome (22q11DS) Anxiety Cell adhesion Dendritic spine |
| url | https://doi.org/10.1186/s13578-023-01081-9 |
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