Capicua Regulates Dendritic Morphogenesis Through Ets in Hippocampal Neurons in vitro

Capicua (Cic), a transcriptional repressor frequently mutated in brain cancer oligodendroglioma, is highly expressed in adult neurons. However, its function in the dendritic growth of neurons in the hippocampus remains poorly understood. Here, we confirmed that Cic was expressed in hippocampal neuro...

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Main Authors: Keqin Li, Shuai Shao, Tongjie Ji, Min Liu, Lufeng Wang, Ying Pang, Mu Chen, Siyi Xu, Kuiming Zhang, Qi Wang, Zhongwei Zhuang, Liang Wei, Yanfei Zhang, Yanlin Chen, Yang Wang, Jing Zhang, Kui Chen, Hao Lian, Chunlong Zhong
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Neuroanatomy
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnana.2021.669310/full
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author Keqin Li
Shuai Shao
Tongjie Ji
Min Liu
Lufeng Wang
Ying Pang
Mu Chen
Siyi Xu
Kuiming Zhang
Qi Wang
Zhongwei Zhuang
Liang Wei
Yanfei Zhang
Yanlin Chen
Yang Wang
Jing Zhang
Kui Chen
Hao Lian
Chunlong Zhong
author_facet Keqin Li
Shuai Shao
Tongjie Ji
Min Liu
Lufeng Wang
Ying Pang
Mu Chen
Siyi Xu
Kuiming Zhang
Qi Wang
Zhongwei Zhuang
Liang Wei
Yanfei Zhang
Yanlin Chen
Yang Wang
Jing Zhang
Kui Chen
Hao Lian
Chunlong Zhong
author_sort Keqin Li
collection DOAJ
description Capicua (Cic), a transcriptional repressor frequently mutated in brain cancer oligodendroglioma, is highly expressed in adult neurons. However, its function in the dendritic growth of neurons in the hippocampus remains poorly understood. Here, we confirmed that Cic was expressed in hippocampal neurons during the main period of dendritogenesis, suggesting that Cic has a function in dendrite growth. Loss-of-function and gain-of function assays indicated that Cic plays a central role in the inhibition of dendritic morphogenesis and dendritic spines in vitro. Further studies showed that overexpression of Cic reduced the expression of Ets in HT22 cells, while in vitro knockdown of Cic in hippocampal neurons significantly elevated the expression of Ets. These results suggest that Cic may negatively control dendrite growth through Ets, which was confirmed by ShRNA knockdown of either Etv4 or Etv5 abolishing the phenotype of Cic knockdown in cultured neurons. Taken together, our results suggest that Cic inhibits dendritic morphogenesis and the growth of dendritic spines through Ets.
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spelling doaj.art-5918075d2328459e9ed8f90301d4fe9e2022-12-21T18:28:29ZengFrontiers Media S.A.Frontiers in Neuroanatomy1662-51292021-07-011510.3389/fnana.2021.669310669310Capicua Regulates Dendritic Morphogenesis Through Ets in Hippocampal Neurons in vitroKeqin Li0Shuai Shao1Tongjie Ji2Min Liu3Lufeng Wang4Ying Pang5Mu Chen6Siyi Xu7Kuiming Zhang8Qi Wang9Zhongwei Zhuang10Liang Wei11Yanfei Zhang12Yanlin Chen13Yang Wang14Jing Zhang15Kui Chen16Hao Lian17Chunlong Zhong18Department of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Emergency, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaCapicua (Cic), a transcriptional repressor frequently mutated in brain cancer oligodendroglioma, is highly expressed in adult neurons. However, its function in the dendritic growth of neurons in the hippocampus remains poorly understood. Here, we confirmed that Cic was expressed in hippocampal neurons during the main period of dendritogenesis, suggesting that Cic has a function in dendrite growth. Loss-of-function and gain-of function assays indicated that Cic plays a central role in the inhibition of dendritic morphogenesis and dendritic spines in vitro. Further studies showed that overexpression of Cic reduced the expression of Ets in HT22 cells, while in vitro knockdown of Cic in hippocampal neurons significantly elevated the expression of Ets. These results suggest that Cic may negatively control dendrite growth through Ets, which was confirmed by ShRNA knockdown of either Etv4 or Etv5 abolishing the phenotype of Cic knockdown in cultured neurons. Taken together, our results suggest that Cic inhibits dendritic morphogenesis and the growth of dendritic spines through Ets.https://www.frontiersin.org/articles/10.3389/fnana.2021.669310/fullcapicuatranscriptional repressordendritic growthspine growthEts factors
spellingShingle Keqin Li
Shuai Shao
Tongjie Ji
Min Liu
Lufeng Wang
Ying Pang
Mu Chen
Siyi Xu
Kuiming Zhang
Qi Wang
Zhongwei Zhuang
Liang Wei
Yanfei Zhang
Yanlin Chen
Yang Wang
Jing Zhang
Kui Chen
Hao Lian
Chunlong Zhong
Capicua Regulates Dendritic Morphogenesis Through Ets in Hippocampal Neurons in vitro
Frontiers in Neuroanatomy
capicua
transcriptional repressor
dendritic growth
spine growth
Ets factors
title Capicua Regulates Dendritic Morphogenesis Through Ets in Hippocampal Neurons in vitro
title_full Capicua Regulates Dendritic Morphogenesis Through Ets in Hippocampal Neurons in vitro
title_fullStr Capicua Regulates Dendritic Morphogenesis Through Ets in Hippocampal Neurons in vitro
title_full_unstemmed Capicua Regulates Dendritic Morphogenesis Through Ets in Hippocampal Neurons in vitro
title_short Capicua Regulates Dendritic Morphogenesis Through Ets in Hippocampal Neurons in vitro
title_sort capicua regulates dendritic morphogenesis through ets in hippocampal neurons in vitro
topic capicua
transcriptional repressor
dendritic growth
spine growth
Ets factors
url https://www.frontiersin.org/articles/10.3389/fnana.2021.669310/full
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