Functional Role of SIL1 in Neurodevelopment and Learning
Background. Sil1 is the causative gene of Marinesco-Sjӧgren Syndrome (MSS). The mutated Sil1 generates shortened SIL1 protein which will form aggregation and be degraded rapidly. Mental retardation is a major symptom of MSS which suggests a role of SIL1 in the development of the central nervous syst...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-01-01
|
| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2019/9653024 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832561109212594176 |
|---|---|
| author | Shilian Xu Jia Zhu Kai Mi Yan Shen Xiaomin Zhang |
| author_facet | Shilian Xu Jia Zhu Kai Mi Yan Shen Xiaomin Zhang |
| author_sort | Shilian Xu |
| collection | DOAJ |
| description | Background. Sil1 is the causative gene of Marinesco-Sjӧgren Syndrome (MSS). The mutated Sil1 generates shortened SIL1 protein which will form aggregation and be degraded rapidly. Mental retardation is a major symptom of MSS which suggests a role of SIL1 in the development of the central nervous system, but how SIL1 functions remains unclear. Objectives. The aim of this study is to explore the role of SIL1 in regulating cerebral development and its underlying molecular mechanism. Methods. The basic expression pattern of SIL1 in tissues and cultured cortical neurons is measured by immunostaining and Western blot. The expression of SIL1 is reduced in vitro and in vivo through RNA interference delivered by a lentivirus. The expression of NMDA receptor subunits and the function of the Reelin signaling pathway are then examined by surface biotinylation and Western blot subsequently. Finally, the spatial learning of young mice was assessed by the Barnes maze task. Results. SIL1 deficiency caused a diminished expression of both Reelin receptors and therefore impaired the Reelin signaling pathway. It then inhibited the developmental expression of GluN2A and impaired the spatial learning of 5-week-old mice. Conclusions. These results suggested that SIL1 is required for the development of the central nervous system which is associated with its role in Reelin signaling. |
| format | Article |
| id | doaj-art-b4b7a0a05a91462d807018a4618a5323 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-b4b7a0a05a91462d807018a4618a53232025-02-03T01:25:56ZengWileyNeural Plasticity2090-59041687-54432019-01-01201910.1155/2019/96530249653024Functional Role of SIL1 in Neurodevelopment and LearningShilian Xu0Jia Zhu1Kai Mi2Yan Shen3Xiaomin Zhang4Department of Physiology, School of Basic Medicine, Kunming Medical University, Kunming, Yunnan Province, ChinaDepartment of Pathology, Institute of Diabetes and Nerve Disease, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing University, Jiaxing, Zhejiang Province, ChinaDepartment of Physiology, School of Basic Medicine, Kunming Medical University, Kunming, Yunnan Province, ChinaDepartment of Physiology, School of Basic Medicine, Kunming Medical University, Kunming, Yunnan Province, ChinaDepartment of Physiology, School of Basic Medicine, Kunming Medical University, Kunming, Yunnan Province, ChinaBackground. Sil1 is the causative gene of Marinesco-Sjӧgren Syndrome (MSS). The mutated Sil1 generates shortened SIL1 protein which will form aggregation and be degraded rapidly. Mental retardation is a major symptom of MSS which suggests a role of SIL1 in the development of the central nervous system, but how SIL1 functions remains unclear. Objectives. The aim of this study is to explore the role of SIL1 in regulating cerebral development and its underlying molecular mechanism. Methods. The basic expression pattern of SIL1 in tissues and cultured cortical neurons is measured by immunostaining and Western blot. The expression of SIL1 is reduced in vitro and in vivo through RNA interference delivered by a lentivirus. The expression of NMDA receptor subunits and the function of the Reelin signaling pathway are then examined by surface biotinylation and Western blot subsequently. Finally, the spatial learning of young mice was assessed by the Barnes maze task. Results. SIL1 deficiency caused a diminished expression of both Reelin receptors and therefore impaired the Reelin signaling pathway. It then inhibited the developmental expression of GluN2A and impaired the spatial learning of 5-week-old mice. Conclusions. These results suggested that SIL1 is required for the development of the central nervous system which is associated with its role in Reelin signaling.http://dx.doi.org/10.1155/2019/9653024 |
| spellingShingle | Shilian Xu Jia Zhu Kai Mi Yan Shen Xiaomin Zhang Functional Role of SIL1 in Neurodevelopment and Learning Neural Plasticity |
| title | Functional Role of SIL1 in Neurodevelopment and Learning |
| title_full | Functional Role of SIL1 in Neurodevelopment and Learning |
| title_fullStr | Functional Role of SIL1 in Neurodevelopment and Learning |
| title_full_unstemmed | Functional Role of SIL1 in Neurodevelopment and Learning |
| title_short | Functional Role of SIL1 in Neurodevelopment and Learning |
| title_sort | functional role of sil1 in neurodevelopment and learning |
| url | http://dx.doi.org/10.1155/2019/9653024 |
| work_keys_str_mv | AT shilianxu functionalroleofsil1inneurodevelopmentandlearning AT jiazhu functionalroleofsil1inneurodevelopmentandlearning AT kaimi functionalroleofsil1inneurodevelopmentandlearning AT yanshen functionalroleofsil1inneurodevelopmentandlearning AT xiaominzhang functionalroleofsil1inneurodevelopmentandlearning |