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SNIP1 and PRC2 coordinate cell fates of neural progenitors during brain development

Author

Listed:
  • Yurika Matsui

    (St. Jude Children’s Research Hospital)

  • Mohamed Nadhir Djekidel

    (St. Jude Children’s Research Hospital)

  • Katherine Lindsay

    (St. Jude Children’s Research Hospital)

  • Parimal Samir

    (St. Jude Children’s Research Hospital
    University of Texas Medical Branch)

  • Nina Connolly

    (St. Jude Children’s Research Hospital)

  • Gang Wu

    (St. Jude Children’s Research Hospital)

  • Xiaoyang Yang

    (St. Jude Children’s Research Hospital)

  • Yiping Fan

    (St. Jude Children’s Research Hospital)

  • Beisi Xu

    (St. Jude Children’s Research Hospital)

  • Jamy C. Peng

    (St. Jude Children’s Research Hospital)

Abstract

Stem cell survival versus death is a developmentally programmed process essential for morphogenesis, sizing, and quality control of genome integrity and cell fates. Cell death is pervasive during development, but its programming is little known. Here, we report that Smad nuclear interacting protein 1 (SNIP1) promotes neural progenitor cell survival and neurogenesis and is, therefore, integral to brain development. The SNIP1-depleted brain exhibits dysplasia with robust induction of caspase 9-dependent apoptosis. Mechanistically, SNIP1 regulates target genes that promote cell survival and neurogenesis, and its activities are influenced by TGFβ and NFκB signaling pathways. Further, SNIP1 facilitates the genomic occupancy of Polycomb complex PRC2 and instructs H3K27me3 turnover at target genes. Depletion of PRC2 is sufficient to reduce apoptosis and brain dysplasia and to partially restore genetic programs in the SNIP1-depleted brain in vivo. These findings suggest a loci-specific regulation of PRC2 and H3K27 marks to toggle cell survival and death in the developing brain.

Suggested Citation

  • Yurika Matsui & Mohamed Nadhir Djekidel & Katherine Lindsay & Parimal Samir & Nina Connolly & Gang Wu & Xiaoyang Yang & Yiping Fan & Beisi Xu & Jamy C. Peng, 2023. "SNIP1 and PRC2 coordinate cell fates of neural progenitors during brain development," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40487-4
    DOI: 10.1038/s41467-023-40487-4
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    References listed on IDEAS

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    2. Myron K. Evans & Yurika Matsui & Beisi Xu & Catherine Willis & Jennifer Loome & Luis Milburn & Yiping Fan & Vishwajeeth Pagala & Jamy C. Peng, 2020. "Ybx1 fine-tunes PRC2 activities to control embryonic brain development," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
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