Wnt信号通路
神经发生
海马结构
生物
染色质
神经科学
齿状回
细胞生物学
细胞命运测定
海马体
神经干细胞
表观遗传学
遗传学
信号转导
干细胞
基因
转录因子
作者
Bo Zhang,Chen Zhao,Wenchen Shen,Wei Li,Yue Zheng,Xiangfei Kong,Junbao Wang,Xudong Wu,Tao Zeng,Ying Liu,Yan Zhou
标识
DOI:10.1038/s41467-023-42322-2
摘要
Abstract The hippocampus plays major roles in learning and memory, and its formation requires precise coordination of patterning, cell proliferation, differentiation, and migration. Here we removed the chromatin-association capability of KDM2B in the progenitors of developing dorsal telencephalon ( Kdm2b ∆CxxC ) to discover that Kdm2b ∆CxxC hippocampus, particularly the dentate gyrus, became drastically smaller with disorganized cellular components and structure. Kdm2b ∆CxxC mice display prominent defects in spatial memory, motor learning and fear conditioning, resembling patients with KDM2B mutations. The migration and differentiation of neural progenitor cells is greatly impeded in the developing Kdm2b ∆CxxC hippocampus. Mechanism studies reveal that Wnt signaling genes in developing Kdm2b ∆CxxC hippocampi are de-repressed due to reduced enrichment of repressive histone marks by polycomb repressive complexes. Activating the Wnt signaling disturbs hippocampal neurogenesis, recapitulating the effect of KDM2B loss. Together, we unveil a previously unappreciated gene repressive program mediated by KDM2B that controls progressive fate specifications and cell migration, hence morphogenesis of the hippocampus.
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