Li Junjie, Jiang Hanyang, Mu Yawei, Wei Zixuan, Ma Ankangzhi, Sun Menghan, Zhao Jingjing, Zhu Cuiqing, Chen Xianhua
State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.
Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, PR China.
iScience. 2023 Jun 7;26(7):107042. doi: 10.1016/j.isci.2023.107042. eCollection 2023 Jul 21.
Alternative pre-mRNA splicing plays critical roles in brain development. SRSF10 is a splicing factor highly expressed in central nervous system and plays important roles in maintaining normal brain functions. However, its role in neural development is unclear. In this study, by conditional depleting SRSF10 in neural progenitor cells (NPCs) and , we found that dysfunction of SRSF10 leads to developmental defects of the brain, which manifest as abnormal ventricle enlargement and cortical thinning anatomically, as well as decreased NPCs proliferation and weakened cortical neurogenesis histologically. Furthermore, we proved that the function of SRSF10 on NPCs proliferation involved the regulation of PI3K-AKT-mTOR-CCND2 pathway and the alternative splicing of , a gene encoding isoforms of cell cycle regulators. These findings highlight the necessity of SRSF10 in the formation of a structurally and functionally normal brain.
可变前体mRNA剪接在大脑发育中起关键作用。SRSF10是一种在中枢神经系统中高度表达的剪接因子,在维持正常脑功能中起重要作用。然而,其在神经发育中的作用尚不清楚。在本研究中,通过在神经祖细胞(NPCs)中条件性缺失SRSF10,我们发现SRSF10功能障碍导致大脑发育缺陷,在解剖学上表现为脑室异常扩大和皮质变薄,在组织学上表现为NPCs增殖减少和皮质神经发生减弱。此外,我们证明SRSF10对NPCs增殖的功能涉及PI3K-AKT-mTOR-CCND2通路的调节以及一个编码细胞周期调节因子异构体的基因的可变剪接。这些发现突出了SRSF10在形成结构和功能正常的大脑中的必要性。