中南大学郭辉小组取得一项新突破。他们探明了Csde1通过细胞周期转录后调控介导神经发生。相关论文于2025年6月24日发表在《神经科学通报》杂志上。

在这项研究中，小组证明在小鼠皮质发育过程中敲除Csde1会导致神经祖细胞增殖受损，导致皮质层压异常和胚胎致死。转录组学分析显示，Csde1上调了参与细胞周期网络的基因的转录。应用双胸腺嘧啶标记方法，该研究组进一步发现csde1基因敲除小鼠神经元祖细胞的细胞周期持续时间延长，G1期明显延长。与CLIP-seq数据的交叉表明，Csde1结合到编码细胞周期基因的mRNA转录本的3'非翻译区（UTR）。特别是，该研究团队发现Csde1直接结合编码Cdk6的mRNA转录本的3' UTR， Cdk6是调节细胞周期从G1期向S期转变的关键基因，从而保持其稳定性。总之，本研究阐明了Csde1作为Cdk6的一种新的调节因子，揭示了其在协调大脑发育中的关键作用，并强调了Csde1突变如何促进神经精神疾病的发病机制。

研究人员表示，CSDE1的功能丧失变体与神经精神疾病密切相关，但CSDE1在神经发生中的确切作用仍不清楚。

附：英文原文

Title: Csde1 Mediates Neurogenesis via Post-transcriptional Regulation of the Cell Cycle

Author: Jia, Xiangbin, Xie, Wenqi, Du, Bing, He, Mei, Chen, Jia, Chen, Meilin, Zhang, Ge, Wang, Ke, Xu, Wanjing, Liao, Yuxin, Tan, Senwei, Lyu, Yongqing, Yu, Bin, Zheng, Zihang, Sun, Xiaoyue, Liao, Yang, Hu, Zhengmao, Yuan, Ling, Tan, Jieqiong, Xia, Kun, Guo, Hui

Issue&Volume: 2025-06-24

Abstract: Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3′ untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3′ UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.

DOI: 10.1007/s12264-025-01426-z

Source: https://link.springer.com/article/10.1007/s12264-025-01426-z