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Capicua Regulates Dendritic Morphogenesis Through Ets in Hippocampal Neurons in Vitro
Frontiers in Neuroanatomy ( IF 2.9 ) Pub Date : 2021-06-28 , DOI: 10.3389/fnana.2021.669310
Keqin Li 1 , Shuai Shao 2 , Tongjie Ji 1 , Min Liu 1 , Lufeng Wang 3 , Ying Pang 1 , Mu Chen 1 , Siyi Xu 1 , Kuiming Zhang 1 , Qi Wang 1 , Zhongwei Zhuang 1 , Liang Wei 1 , Yanfei Zhang 1 , Yanlin Chen 2 , Yang Wang 4 , Jing Zhang 1 , Kui Chen 1 , Hao Lian 1 , Chunlong Zhong 1
Affiliation  

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.

中文翻译:

Capicua 通过体外海马神经元中的 Ets 调节树突形态发生

Capicua (Cic) 是一种在脑癌少突胶质细胞瘤中经常发生突变的转录抑制因子,在成人神经元中高度表达。然而,其在海马神经元树突状生长中的功能仍然知之甚少。在这里,我们证实了 Cic 在树突形成的主要时期在海马神经元中表达,表明 Cic 在树突生长中具有功能。功能丧失和功能获得试验表明 Cic 在体外抑制树突形态发生和树突棘中起核心作用。进一步的研究表明,Cic 的过表达降低了 HT22 细胞中 Ets 的表达,而海马神经元中 Cic 的体外敲低显着提高了 Ets 的表达。这些结果表明 Cic 可能通过 Ets 负向控制枝晶生长,Etv4 或 Etv5 的 ShRNA 敲低消除了培养神经元中 Cic 敲低的表型,证实了这一点。总之,我们的结果表明 Cic 通过 Ets 抑制树突形态发生和树突棘的生长。
更新日期:2021-06-28
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