SRSF10 regulates proliferation of neural progenitor cells and affects neurogenesis in developing mouse neocortex

Junjie Li; Hanyang Jiang; Yawei Mu; Zixuan Wei; Ankangzhi Ma; Menghan Sun; Jingjing Zhao; Cuiqing Zhu; Xianhua Chen

doi:10.1016/j.isci.2023.107042

SRSF10 regulates proliferation of neural progenitor cells and affects neurogenesis in developing mouse neocortex

iScience. 2023 Jun 7;26(7):107042. doi: 10.1016/j.isci.2023.107042. eCollection 2023 Jul 21.

Authors

Junjie Li¹, Hanyang Jiang¹, Yawei Mu¹, Zixuan Wei¹, Ankangzhi Ma¹, Menghan Sun¹, Jingjing Zhao², Cuiqing Zhu¹, Xianhua Chen¹

Affiliations

¹ State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.
² Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, PR China.

Abstract

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) in vivo and in vitro, 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 Nasp, 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.

Keywords: Cell biology; Developmental neuroscience; Neuroscience.