Posttranscriptional Control of Neural Progenitors Temporal Dynamics During Neocortical Development by Syncrip
Abstract The development of the mammalian neocortex is precisely regulated by temporal gene expression, yet the temporal regulatory mechanisms of cortical neurogenesis, particularly how radial glial cells (RGCs) sequentially generate deep to superficial neurons, remain unclear. Here, the hnRNP famil...
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| Format: | Article |
| Language: | English |
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202411732 |
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| author | Jiarui Wu Haoyang Yu Xinyi Dou Bin Yin Lin Hou Yuanchao Xue Boqin Qiang Pengcheng Shu Xiaozhong Peng |
| author_facet | Jiarui Wu Haoyang Yu Xinyi Dou Bin Yin Lin Hou Yuanchao Xue Boqin Qiang Pengcheng Shu Xiaozhong Peng |
| author_sort | Jiarui Wu |
| collection | DOAJ |
| description | Abstract The development of the mammalian neocortex is precisely regulated by temporal gene expression, yet the temporal regulatory mechanisms of cortical neurogenesis, particularly how radial glial cells (RGCs) sequentially generate deep to superficial neurons, remain unclear. Here, the hnRNP family member Syncrip (hnRNP Q) is identified as a key modulator of superficial neuronal differentiation in neocortical neurogenesis. Syncrip knockout in RGCs disrupts differentiation and abnormal neuronal localization, ultimately resulting in superficial cortical layer defects as well as learning and memory impairments in mice. Single‐cell RNA sequencing analysis demonstrated that the knockout of Syncrip disrupts the late‐stage neurogenesis, stalling transcriptional progression in RGCs. Mechanistically, Syncrip maintains the transcription of temporal process‐related transcription factors by recruiting stabilization complexes through phase separation, crucially regulating the Notch signaling pathway that determines the fate of RGCs. Furthermore, pathogenic human mutations in Syncrip weaken its phase‐separation capability, failing to form stable complexes normally. Thus, Syncrip acts as a mediator of posttranscriptional regulatory mechanisms, governing the fate progression of RGCs and the advancement of intrinsic temporal programs. This study establishes an intracellular mechanism for posttranscriptional regulation of progressive fate determination in cortical neurogenesis. |
| format | Article |
| id | doaj-art-834fd38f2bab46db85ba1b402ce9fe25 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-834fd38f2bab46db85ba1b402ce9fe252025-08-20T03:49:36ZengWileyAdvanced Science2198-38442025-02-01128n/an/a10.1002/advs.202411732Posttranscriptional Control of Neural Progenitors Temporal Dynamics During Neocortical Development by SyncripJiarui Wu0Haoyang Yu1Xinyi Dou2Bin Yin3Lin Hou4Yuanchao Xue5Boqin Qiang6Pengcheng Shu7Xiaozhong Peng8State Key Laboratory of Common Mechanism Research for Major Diseases Department of Biochemistry & Molecular Biology Medical Primate Research Center Neuroscience Center Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College Beijing 100005 ChinaState Key Laboratory of Common Mechanism Research for Major Diseases Department of Biochemistry & Molecular Biology Medical Primate Research Center Neuroscience Center Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College Beijing 100005 ChinaState Key Laboratory of Common Mechanism Research for Major Diseases Department of Biochemistry & Molecular Biology Medical Primate Research Center Neuroscience Center Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College Beijing 100005 ChinaState Key Laboratory of Common Mechanism Research for Major Diseases Department of Biochemistry & Molecular Biology Medical Primate Research Center Neuroscience Center Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College Beijing 100005 ChinaState Key Laboratory of Common Mechanism Research for Major Diseases Department of Biochemistry & Molecular Biology Medical Primate Research Center Neuroscience Center Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College Beijing 100005 ChinaKey Laboratory of RNA Biology Institute of Biophysics Chinese Academy of Sciences Beijing 100101 ChinaState Key Laboratory of Common Mechanism Research for Major Diseases Department of Biochemistry & Molecular Biology Medical Primate Research Center Neuroscience Center Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College Beijing 100005 ChinaState Key Laboratory of Common Mechanism Research for Major Diseases Department of Biochemistry & Molecular Biology Medical Primate Research Center Neuroscience Center Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College Beijing 100005 ChinaState Key Laboratory of Common Mechanism Research for Major Diseases Department of Biochemistry & Molecular Biology Medical Primate Research Center Neuroscience Center Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College Beijing 100005 ChinaAbstract The development of the mammalian neocortex is precisely regulated by temporal gene expression, yet the temporal regulatory mechanisms of cortical neurogenesis, particularly how radial glial cells (RGCs) sequentially generate deep to superficial neurons, remain unclear. Here, the hnRNP family member Syncrip (hnRNP Q) is identified as a key modulator of superficial neuronal differentiation in neocortical neurogenesis. Syncrip knockout in RGCs disrupts differentiation and abnormal neuronal localization, ultimately resulting in superficial cortical layer defects as well as learning and memory impairments in mice. Single‐cell RNA sequencing analysis demonstrated that the knockout of Syncrip disrupts the late‐stage neurogenesis, stalling transcriptional progression in RGCs. Mechanistically, Syncrip maintains the transcription of temporal process‐related transcription factors by recruiting stabilization complexes through phase separation, crucially regulating the Notch signaling pathway that determines the fate of RGCs. Furthermore, pathogenic human mutations in Syncrip weaken its phase‐separation capability, failing to form stable complexes normally. Thus, Syncrip acts as a mediator of posttranscriptional regulatory mechanisms, governing the fate progression of RGCs and the advancement of intrinsic temporal programs. This study establishes an intracellular mechanism for posttranscriptional regulation of progressive fate determination in cortical neurogenesis.https://doi.org/10.1002/advs.202411732neocortexneural progenitorsneurodevelopment disordersphase separationposttranscriptional regulationsyncrip |
| spellingShingle | Jiarui Wu Haoyang Yu Xinyi Dou Bin Yin Lin Hou Yuanchao Xue Boqin Qiang Pengcheng Shu Xiaozhong Peng Posttranscriptional Control of Neural Progenitors Temporal Dynamics During Neocortical Development by Syncrip Advanced Science neocortex neural progenitors neurodevelopment disorders phase separation posttranscriptional regulation syncrip |
| title | Posttranscriptional Control of Neural Progenitors Temporal Dynamics During Neocortical Development by Syncrip |
| title_full | Posttranscriptional Control of Neural Progenitors Temporal Dynamics During Neocortical Development by Syncrip |
| title_fullStr | Posttranscriptional Control of Neural Progenitors Temporal Dynamics During Neocortical Development by Syncrip |
| title_full_unstemmed | Posttranscriptional Control of Neural Progenitors Temporal Dynamics During Neocortical Development by Syncrip |
| title_short | Posttranscriptional Control of Neural Progenitors Temporal Dynamics During Neocortical Development by Syncrip |
| title_sort | posttranscriptional control of neural progenitors temporal dynamics during neocortical development by syncrip |
| topic | neocortex neural progenitors neurodevelopment disorders phase separation posttranscriptional regulation syncrip |
| url | https://doi.org/10.1002/advs.202411732 |
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