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

• Published in: iScience 2023-07, Vol.26 (7), p.107042-107042, Article 107042
• Main Authors: Li, Junjie, Jiang, Hanyang, Mu, Yawei, Wei, Zixuan, Ma, Ankangzhi, Sun, Menghan, Zhao, Jingjing, Zhu, Cuiqing, Chen, Xianhua
• Format: Article
• Language: English
• Subjects: Cell biology; Developmental neuroscience; Neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.107042

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. [Display omitted] •SRSF10 knockout in NPCs causes dilated ventricle and thinned cortex in mouse brain•Dysfunction of SRSF10 inhibits NPCs proliferation and causes cell cycle abnormal•SRSF10 knockdown inhibits PI3K-AKT-mTOR-CCND2-signaling pathway in NPCs•SRSF10 knockdown alters the alternative splicing of Nasp exon 7 in NPCs Neuroscience; Developmental neuroscience; Cell biology