1. Developmental Biology
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The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline

  1. Alexis S Bailey
  2. Pedro J Batista
  3. Rebecca S Gold
  4. Y Grace Chen
  5. Dirk G de Rooij
  6. Howard Y Chang
  7. Margaret T Fuller  Is a corresponding author
  1. Stanford University School of Medicine, United States
  2. University of Amsterdam, Netherlands
Research Article
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Cite this article as: eLife 2017;6:e26116 doi: 10.7554/eLife.26116

Abstract

The switch from mitosis to meiosis is the key event marking onset of differentiation in the germline stem cell lineage. In Drosophila, the translational repressor Bgcn is required for spermatogonia to stop mitosis and transition to meiotic prophase and the spermatocyte state. Here we show that the mammalian Bgcn ortholog YTHDC2 facilitates a clean switch from mitosis to meiosis in mouse germ cells, revealing a conserved role for YTHDC2 in this critical cell fate transition. YTHDC2-deficient male germ cells enter meiosis but have a mixed identity, maintaining expression of Cyclin A2 and failing to properly express many meiotic markers. Instead of continuing through meiotic prophase, the cells attempt an abnormal mitotic-like division and die. YTHDC2 binds multiple transcripts including Ccna2 and other mitotic transcripts, binds specific piRNA precursors, and interacts with RNA granule components, suggesting that proper progression of germ cells through meiosis is licensed by YTHDC2 through post-transcriptional regulation.

Article and author information

Author details

  1. Alexis S Bailey

    Department of Developmental Biology, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Pedro J Batista

    Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Rebecca S Gold

    Department of Developmental Biology, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Y Grace Chen

    Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Dirk G de Rooij

    Center for Reproductive Medicine, University of Amsterdam, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Howard Y Chang

    Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Margaret T Fuller

    Department of Developmental Biology, Stanford University School of Medicine, Stanford, United States
    For correspondence
    mtfuller@stanford.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3804-4987

Funding

National Institutes of Health (NIH T32 HD007249)

  • Alexis S Bailey

Lalor Foundation (Postdoctoral Fellowship)

  • Alexis S Bailey

National Cancer Institute (Intramural Research Program of the NIH)

  • Pedro J Batista

National Institutes of Health (NIH R01 HG004361)

  • Howard Y Chang

Reed-Hodgson Professorship

  • Margaret T Fuller

National Institutes of Health (NIH P50 HD068158)

  • Margaret T Fuller

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health (NIH). All of the experiments were approved by the Stanford University Animal Care and Use Committee (IACUC), protocol (#21656).

Human subjects: Human testis sections were obtained from the Fertility Preservation Program of Pittsburgh. Informed consent was obtained and the testicular tissue freezing protocol was approved by the Institutional Review Board of the University of Pittsburgh.

Reviewing Editor

  1. Matthew Freeman, University of Oxford, United Kingdom

Publication history

  1. Received: February 17, 2017
  2. Accepted: October 29, 2017
  3. Accepted Manuscript published: October 31, 2017 (version 1)
  4. Version of Record published: November 27, 2017 (version 2)

Copyright

© 2017, Bailey et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Further reading

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