The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline
- Stanford University School of Medicine, United States
- University of Amsterdam, Netherlands
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.
Data availability
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Regulation of the transition from mitosis to meiosis by the conserved RNA-helicase YTHDC2/BGCNNCBI Gene Expression Omnibus (accession no: GSE93567).
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Poised chromatin and bivalent domains facilitate the mitosis-to-meiosis transition in the male germlineNCBI Gene Expression Omnibus (accession no: GSE69946).
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Cellular source and mechanisms of high transcriptome complexity in the mammalian testis (RNA-Seq cells)NCBI Gene Expression Omnibus (accession no: GSE43717).
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RNA-Seq and RNA Polymerase II ChIP-Seq of mouse spermatogenesisNCBI Gene Expression Omnibus (accession no: GSE44346).
Article and author information
Author details
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.
Reviewing Editor
- Matthew Freeman, University of Oxford, United Kingdom
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.
Version history
- Received: February 17, 2017
- Accepted: October 29, 2017
- Accepted Manuscript published: October 31, 2017 (version 1)
- 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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The conserved RNA helicase YTHDC2 regulates the transition from proliferation to differentiation in the germline
eLife 6:e26116.
https://doi.org/10.7554/eLife.26116
Further reading
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- Developmental Biology
Large-scale cell flow characterizes gastrulation in animal development. In amniote gastrulation, particularly in avian gastrula, a bilateral vortex-like counter-rotating cell flow, called ‘polonaise movements’, appears along the midline. Here, through experimental manipulations, we addressed relationships between the polonaise movements and morphogenesis of the primitive streak, the earliest midline structure in amniotes. Suppression of the Wnt/planar cell polarity (PCP) signaling pathway maintains the polonaise movements along a deformed primitive streak. Mitotic arrest leads to diminished extension and development of the primitive streak and maintains the early phase of the polonaise movements. Ectopically induced Vg1, an axis-inducing morphogen, generates the polonaise movements, aligned to the induced midline, but disturbs the stereotypical cell flow pattern at the authentic midline. Despite the altered cell flow, induction and extension of the primitive streak are preserved along both authentic and induced midlines. Finally, we show that ectopic axis-inducing morphogen, Vg1, is capable of initiating the polonaise movements without concomitant PS extension under mitotic arrest conditions. These results are consistent with a model wherein primitive streak morphogenesis is required for the maintenance of the polonaise movements, but the polonaise movements are not necessarily responsible for primitive streak morphogenesis. Our data describe a previously undefined relationship between the large-scale cell flow and midline morphogenesis in gastrulation.
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- Developmental Biology
- Physics of Living Systems
Geometric criteria can be used to assess whether cell intercalation is active or passive during the convergent extension of tissue.
