生物
神经干细胞
神经发生
核孔蛋白
细胞生物学
祖细胞
祖细胞
干细胞
转录因子
神经发育
基因敲除
染色质
核孔
细胞分化
核运输
遗传学
细胞核
基因
核心
作者
Wenxiu Dai,Zhixiong Liu,Minbiao Yan,Ximing Nian,Hong Fan,Zhihao Zhou,Chaomeng Wang,Xing Fu,Xuewen Li,Mengyun Jiang,Yanqin Zhu,Qiuying Huang,Xiaoyun Lu,Lichao Hou,Ning Yan,Qing K. Wang,Jin Hu,Wei Mo,Xueqin Zhang,Liang Zhang
标识
DOI:10.1016/j.devcel.2024.01.002
摘要
Summary
Mutations or dysregulation of nucleoporins (Nups) are strongly associated with neural developmental diseases, yet the underlying mechanisms remain poorly understood. Here, we show that depletion of Nup Seh1 in radial glial progenitors results in defective neural progenitor proliferation and differentiation that ultimately manifests in impaired neurogenesis and microcephaly. This loss of stem cell proliferation is not associated with defects in the nucleocytoplasmic transport. Rather, transcriptome analysis showed that ablation of Seh1 in neural stem cells derepresses the expression of p21, and knockdown of p21 partially restored self-renewal capacity. Mechanistically, Seh1 cooperates with the NuRD transcription repressor complex at the nuclear periphery to regulate p21 expression. Together, these findings identified that Nups regulate brain development by exerting a chromatin-associated role and affecting neural stem cell proliferation.
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