KDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors.
KDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors.
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KDM2B通过转录沉默神经祖细胞中的Wnt信号调节海马形态发生。
DOI：
10.1038/s41467-023-42322-2
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发表时间：
2023-10-14
影响因子：
16.6
通讯作者：
Zhou, Yan
中科院分区：
文献类型：
--
作者：
Zhang, Bo;Zhao, Chen;Shen, Wenchen;Li, Wei;Zheng, Yue;Kong, Xiangfei;Wang, Junbao;Wu, Xudong;Zeng, Tao;Liu, Ying;Zhou, Yan
海马在学习和记忆中起着重要作用，其形成需要精确协调图案，细胞增殖，分化和迁移。在这里，我们去除了发育中端脑背侧祖细胞（Kdm 2b ️ CxxC）中KDM 2B的染色质结合能力，发现Kdm 2b ️ CxxC海马体，特别是齿状回，变得非常小，细胞成分和结构混乱。Kdm 2b/CxxC小鼠在空间记忆、运动学习和恐惧条件反射方面表现出明显的缺陷，类似于KDM 2B突变的患者。神经前体细胞的迁移和分化在发育中的Kdm 2b → CxxC海马中受到极大阻碍。机制研究表明，发育中的Kdm 2b-CxxC campi中的Wnt信号传导基因由于多梳抑制复合物减少了抑制性组蛋白标记的富集而被去抑制。激活Wnt信号传导干扰海马神经发生，重现KDM 2B丢失的作用。我们一起揭示了一个以前不受重视的基因抑制程序介导的KDM 2B控制渐进的命运规范和细胞迁移，因此海马的形态发生。Zhang等人报道，KDM 2B-CxxC激活发育中的海马中的Wnt信号传导，其中神经祖细胞的迁移和分化被阻断。KDM 2B-CxxC小鼠表现出海马形态学和相关行为的缺陷。
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. Zhang et al. report that KDM2B-∆CxxC activated Wnt signaling in the developing hippocampi, where the migration and differentiation of neural progenitors were blocked. KDM2B-∆CxxC mice exhibited defects of hippocampal morphology and related behaviors.
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影响因子：
7.7
作者：
Farcas AM;Blackledge NP;Sudbery I;Long HK;McGouran JF;Rose NR;Lee S;Sims D;Cerase A;Sheahan TW;Koseki H;Brockdorff N;Ponting CP;Kessler BM;Klose RJ
通讯作者：
Klose RJ
影响因子：
16.6
作者：
Eto H;Kishi Y;Yakushiji-Kaminatsui N;Sugishita H;Utsunomiya S;Koseki H;Gotoh Y
通讯作者：
Gotoh Y
影响因子：
7.7
作者：
Caramello A;Galichet C;Rizzoti K;Lovell-Badge R
通讯作者：
Lovell-Badge R
DOI：
10.1038/s41580-021-00398-y
发表时间：
2021-12
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Blackledge NP;Klose RJ
通讯作者：
Klose RJ
影响因子：
16.2
作者：
Hirabayashi, Yusuke;Suzki, Nao;Gotoh, Yukiko
通讯作者：
Gotoh, Yukiko