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KDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors

Author

Listed:
  • Bo Zhang

    (Zhongnan Hospital of Wuhan University, Wuhan University)

  • Chen Zhao

    (Zhongnan Hospital of Wuhan University, Wuhan University)

  • Wenchen Shen

    (Zhongnan Hospital of Wuhan University, Wuhan University)

  • Wei Li

    (Zhongnan Hospital of Wuhan University, Wuhan University)

  • Yue Zheng

    (Zhongnan Hospital of Wuhan University, Wuhan University)

  • Xiangfei Kong

    (Zhongnan Hospital of Wuhan University, Wuhan University)

  • Junbao Wang

    (Zhongnan Hospital of Wuhan University, Wuhan University)

  • Xudong Wu

    (Tianjin Medical University
    Tianjin Medical University General Hospital)

  • Tao Zeng

    (Tongji University School of Medicine)

  • Ying Liu

    (Zhongnan Hospital of Wuhan University, Wuhan University)

  • Yan Zhou

    (Zhongnan Hospital of Wuhan University, Wuhan University)

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.

Suggested Citation

  • Bo Zhang & Chen Zhao & Wenchen Shen & Wei Li & Yue Zheng & Xiangfei Kong & Junbao Wang & Xudong Wu & Tao Zeng & Ying Liu & Yan Zhou, 2023. "KDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42322-2
    DOI: 10.1038/s41467-023-42322-2
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