Multiscale analysis of single and double maternal-zygotic Myh9 and Myh10 mutants during mouse preimplantation development

Abstract

During the first days of mammalian development, the embryo forms the blastocyst, the structure responsible for implanting the mammalian embryo. Consisting of an epithelium enveloping the pluripotent inner cell mass and a fluid-filled lumen, the blastocyst results from a series of cleavages divisions, morphogenetic movements and lineage specification. Recent studies identified the essential role of actomyosin contractility in driving the cytokinesis, morphogenesis and fate specification leading to the formation of the blastocyst. However, the preimplantation development of contractility mutants has not been characterized. Here, we generated single and double maternal-zygotic mutants of non-muscle myosin II heavy chains (NMHC) to characterize them with multiscale imaging. We find that Myh9 (NMHC II-A) is the major NMHC during preimplantation development as its maternal-zygotic loss causes failed cytokinesis, increased duration of the cell cycle, weaker embryo compaction and reduced differentiation, whereas Myh10 (NMHC II-B) maternal-zygotic loss is much less severe. Double maternal-zygotic mutants for Myh9 and Myh10 show a much stronger phenotype, failing most attempts of cytokinesis. We find that morphogenesis and fate specification are affected but nevertheless carry on in a timely fashion, regardless of the impact of the mutations on cell number. Strikingly, even when all cell divisions fail, the resulting single-celled embryo can initiate trophectoderm differentiation and lumen formation by accumulating fluid in increasingly large vacuoles. Therefore, contractility mutants reveal that fluid accumulation is a cell-autonomous process and that the preimplantation program carries on independently of successful cell division.

Data availability

The microscopy data, ROI and analyses are available on the following repository under a CC BY- NC-SA license: https://ressources.curie.fr/mzmyh/

The following previously published data sets were used

Article and author information

Author details

  1. Markus Frederik Schliffka

    Genetics and developmental biology unit, Institut Curie, Paris, France
    Competing interests
    Markus Frederik Schliffka, M.F.S. is employed by Carl Zeiss SAS via a public PhD programme Conventions Industrielles de Formation par la Recherche (CIFRE) co-funded by the Association Nationale de la Recherche et de la Technologie (ANRT)..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5128-1653
  2. Anna-Francesca Tortorelli

    Genetics and developmental biology unit, Institut Curie, Paris, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9995-9582
  3. Özge Özgüç

    Genetics and developmental biology unit, Institut Curie, Paris, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1545-1715
  4. Ludmilla de Plater

    Genetics and developmental biology unit, Institut Curie, Paris, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0982-5960
  5. Oliver Polzer

    Genetics and developmental biology unit, Institut Curie, Paris, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4970-6058
  6. Diane Pelzer

    Genetics and developmental biology unit, Institut Curie, Paris, France
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6906-2451
  7. Jean-Léon Maître

    Genetics and developmental biology unit, Institut Curie, Paris, France
    For correspondence
    jean-leon.maitre@curie.fr
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3688-1474

Funding

Institut des sciences biologiques

  • Diane Pelzer

Agence Nationale de la Recherche (ANR-11-LABX-0044)

  • Jean-Léon Maître

Agence Nationale de la Recherche (ANR-10-IDEX-0001-02)

  • Jean-Léon Maître

Association Nationale de la Recherche et de la Technologie (2019/0253)

  • Markus Frederik Schliffka

H2020 Marie Skłodowska-Curie Actions (666003)

  • Özge Özgüç

Institut National de la Santé et de la Recherche Médicale

  • Jean-Léon Maître

Fondation pour la Recherche Médicale

  • Özge Özgüç

Fondation Schlumberger pour l'Education et la Recherche

  • Jean-Léon Maître

H2020 European Research Council (ERC-2017-StG 757557)

  • Jean-Léon Maître

European Molecular Biology Organisation

  • Jean-Léon Maître

Université de Recherche Paris Sciences et Lettres (17-CONV-0005)

  • Jean-Léon Maître

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

Reviewing Editor

  1. Edward E Morrisey, University of Pennsylvania, United States

Ethics

Animal experimentation: All animal work is performed in the animal facility at the Institut Curie, with permission by the institutional veterinarian overseeing the operation (APAFIS #11054- 2017082914226001). The animal facilities are operated according to international animal welfare rules.

Version history

  1. Received: March 18, 2021
  2. Accepted: March 28, 2021
  3. Accepted Manuscript published: April 19, 2021 (version 1)
  4. Version of Record published: May 4, 2021 (version 2)
  5. Version of Record updated: March 2, 2022 (version 3)

Copyright

© 2021, Schliffka 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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  1. Markus Frederik Schliffka
  2. Anna-Francesca Tortorelli
  3. Özge Özgüç
  4. Ludmilla de Plater
  5. Oliver Polzer
  6. Diane Pelzer
  7. Jean-Léon Maître
(2021)
Multiscale analysis of single and double maternal-zygotic Myh9 and Myh10 mutants during mouse preimplantation development
eLife 10:e68536.
https://doi.org/10.7554/eLife.68536

Share this article

https://doi.org/10.7554/eLife.68536

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