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The enigmatic meiotic dense body and its newly discovered component, SCML1, are dispensable for fertility and gametogenesis in mice

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Abstract

Meiosis is a critical phase in the life cycle of sexually reproducing organisms. Chromosome numbers are halved during meiosis, which requires meiosis-specific modification of chromosome behaviour. Furthermore, suppression of transposons is particularly important during meiosis to allow the transmission of undamaged genomic information between generations. Correspondingly, specialized genome defence mechanisms and nuclear structures characterize the germ line during meiosis. Survival of mammalian spermatocytes requires that the sex chromosomes form a distinct silenced chromatin domain, called the sex body. An enigmatic spherical DNA-negative structure, called the meiotic dense body, forms in association with the sex body. The dense body contains small non-coding RNAs including microRNAs and PIWI-associated RNAs. These observations gave rise to speculations that the dense body may be involved in sex body formation and or small non-coding RNA functions, e.g. the silencing of transposons. Nevertheless, the function of the dense body has remained mysterious because no protein essential for dense body formation has been reported yet. We discovered that the polycomb-related sex comb on midleg-like 1 (SCML1) is a meiosis-specific protein and is an essential component of the meiotic dense body. Despite abolished dense body formation, Scml1-deficient mice are fertile and proficient in sex body formation, transposon silencing and in timely progression through meiosis and gametogenesis. Thus, we conclude that dense body formation is not an essential component of the gametogenetic program in the mammalian germ line.

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Acknowledgments

We thank Rolf Jessberger for sharing ideas, anti-SYCP3 antibody and departmental support, Mary Ann Handel for histone H1T antibody, Nadine Maiwald for the purification of anti-SCML1 antibodies and Daniel Tränkner for lab support and help with Southern blotting. We thank the DIGS-BB program for supporting I.D. CRTD seed grant supported A.G-R. The Deutsche Forschungsgemeinschaft (DFG; grants: SPP1384:TO421/4-1 and 4–2, TO421/3-1, 3–2, 5–1, 6–1, 7–1, 8–1 and 8–2), and MeDDrive 2010 from the TU Dresden Faculty of Medicine supported F.P., K.D., A.G-R., L.W., I.D. and A.T. IMBA, the Austrian Ministry of Sciences, and the Austrian Academy of Sciences supported J.M.P. Wellcome Trust/Cancer Research UK supported A.S. The Max Planck Society supported B.H. An EFRE grant (EuropäischerFondsfürRegionaleEntwicklung) supported J.F. and A.F.S.

Author contributions

Most experiments were carried out by F.P. (Figs. 2, 3b, c, 4, 5, 6, 7, 8, S2 and S4c, e) and K.D. (Figs. 1, 3a, e, S1 and S4d). K.D. identified and cloned the full-length Scml1 open reading frame, generated anti-SCML1 antibodies, devised experiments together with A.T. and contributed to day-to-day supervision of F.P. and A.R. during the initial stages of characterization of Scml1-deficient mice. The Scml1-deficient ES cells and mice were generated by A.G-R. (Fig. S4a, b) with the assistance and supervision of J-F.F. Further experiments were performed by T.K. (Fig. 3d), L.W. (Supplementary Fig. S3b) and I.D. (Supplementary Fig. S3a). Knockout construct was generated by J.F. and A.F.S.; J.P. supplied FKBP6 antibodies and experimental material; A.S. and B.H. provided support for the discovery of Scml1; A.T. wrote the manuscript. All authors were involved in discussions and commented on the manuscript.

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    Authors and Affiliations

    1. Institute of Physiological Chemistry, Medical Faculty of TU Dresden, Fiedlerstrasse 42, 01307, Dresden, Germany

      Frantzeskos Papanikos, Lukasz Wojtasz, Ihsan Dereli & Attila Toth

    2. Biotechnology Center of the TU Dresden, Tatzberg 47/49, 01307, Dresden, Germany

      Katrin Daniel, Jun Fu & A. Francis Stewart

    3. Department of Human Genetics, Radboud University Medical Center, Geert Grooteplein 10, 6525 GA, Nijmegen, The Netherlands

      Angelique Goercharn-Ramlal

    4. DFG Center for Regenerative Therapies, Dresden (CRTD), Technische Universität Dresden, Dresden, 01307, Germany

      Ji-Feng Fei & Thomas Kurth

    5. Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria

      Josef Penninger

    6. Max Planck Institute of Biochemistry, Martinsried, Germany

      Bianca Habermann

    7. Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK

      Azim Surani

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    1. Frantzeskos Papanikos
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    Correspondence to Attila Toth.

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    All experiments performed in this study involving animals were in accordance with the ethical standards of the Technische Universität Dresden. This article does not contain any studies with human participants performed by any of the authors.

    Funding

    This work was supported by DFG grants: SPP1384:TO421/4-1 and 4-2, TO421/3-1, 3-2, 5-1, 6-1, 7-1, 8–1 and 8-2, MeDDrive 2010 from the TU Dresden Faculty of Medicine, DIGS-BB program, IMBA, the Austrian Ministry of Sciences, and the Austrian Academy of Sciences, Wellcome Trust/Cancer Research UK, The Max Planck Society and an EFRE grant (EuropäischerFondsfürRegionaleEntwicklung).

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    The authors declare that they have no competing interests.

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    Frantzeskos Papanikos, Katrin Daniel and Angelique Goercharn-Ramlal contributed equally to this work.

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    Papanikos, F., Daniel, K., Goercharn-Ramlal, A. et al. The enigmatic meiotic dense body and its newly discovered component, SCML1, are dispensable for fertility and gametogenesis in mice. Chromosoma 126, 399–415 (2017). https://doi.org/10.1007/s00412-016-0598-1

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