Li Keqin, Shao Shuai, Ji Tongjie, Liu Min, Wang Lufeng, Pang Ying, Chen Mu, Xu Siyi, Zhang Kuiming, Wang Qi, Zhuang Zhongwei, Wei Liang, Zhang Yanfei, Chen Yanlin, Wang Yang, Zhang Jing, Chen Kui, Lian Hao, Zhong Chunlong
Department of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Front Neuroanat. 2021 Jul 27;15:669310. doi: 10.3389/fnana.2021.669310. eCollection 2021.
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 . Further studies showed that overexpression of Cic reduced the expression of Ets in HT22 cells, while 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.
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,在成年神经元中高度表达。然而,其在海马体神经元树突生长中的功能仍知之甚少。在此,我们证实Cic在树突发生的主要时期在海马体神经元中表达,这表明Cic在树突生长中具有功能。功能丧失和功能获得实验表明,Cic在抑制树突形态发生和树突棘方面起着核心作用。进一步的研究表明,Cic的过表达降低了HT22细胞中Ets的表达,而海马体神经元中Cic的敲低显著提高了Ets的表达。这些结果表明,Cic可能通过Ets负向控制树突生长,这通过对Etv4或Etv5进行短发夹RNA敲低消除了培养神经元中Cic敲低的表型得到证实。综上所述,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。