1.Csde1 Mediates Neurogenesis via Post-transcriptional Regulation of the Cell Cycle.
Xiangbin JIA ; Wenqi XIE ; Bing DU ; Mei HE ; Jia CHEN ; Meilin CHEN ; Ge ZHANG ; Ke WANG ; Wanjing XU ; Yuxin LIAO ; Senwei TAN ; Yongqing LYU ; Bin YU ; Zihang ZHENG ; Xiaoyue SUN ; Yang LIAO ; Zhengmao HU ; Ling YUAN ; Jieqiong TAN ; Kun XIA ; Hui GUO
Neuroscience Bulletin 2025;41(11):1977-1990
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.
Animals
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Neurogenesis/genetics*
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Cell Cycle/genetics*
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Mice, Knockout
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Mice
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Neural Stem Cells/metabolism*
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DNA-Binding Proteins/metabolism*
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Cyclin-Dependent Kinase 6/genetics*
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Cell Proliferation
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3' Untranslated Regions
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Cerebral Cortex/embryology*
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RNA-Binding Proteins
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Mice, Inbred C57BL
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