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Placentation defects are highly prevalent in embryonic lethal mouse mutants

Author

Listed:
  • Vicente Perez-Garcia

    (The Babraham Institute, Babraham Research Campus
    Centre for Trophoblast Research, University of Cambridge)

  • Elena Fineberg

    (The Babraham Institute, Babraham Research Campus
    Centre for Trophoblast Research, University of Cambridge)

  • Robert Wilson

    (The Francis Crick Institute)

  • Alexander Murray

    (The Babraham Institute, Babraham Research Campus
    Centre for Trophoblast Research, University of Cambridge)

  • Cecilia Icoresi Mazzeo

    (Wellcome Trust Sanger Institute)

  • Catherine Tudor

    (Wellcome Trust Sanger Institute)

  • Arnold Sienerth

    (The Babraham Institute, Babraham Research Campus
    Centre for Trophoblast Research, University of Cambridge)

  • Jacqueline K. White

    (Wellcome Trust Sanger Institute)

  • Elizabeth Tuck

    (Wellcome Trust Sanger Institute)

  • Edward J. Ryder

    (Wellcome Trust Sanger Institute)

  • Diane Gleeson

    (Wellcome Trust Sanger Institute)

  • Emma Siragher

    (Wellcome Trust Sanger Institute)

  • Hannah Wardle-Jones

    (Wellcome Trust Sanger Institute)

  • Nicole Staudt

    (Wellcome Trust Sanger Institute)

  • Neha Wali

    (Wellcome Trust Sanger Institute)

  • John Collins

    (Wellcome Trust Sanger Institute)

  • Stefan Geyer

    (Center for Anatomy & Cell Biology, Medical University of Vienna)

  • Elisabeth M. Busch-Nentwich

    (Wellcome Trust Sanger Institute
    University of Cambridge)

  • Antonella Galli

    (Wellcome Trust Sanger Institute)

  • James C. Smith

    (The Francis Crick Institute)

  • Elizabeth Robertson

    (Sir William Dunn School of Pathology, University of Oxford)

  • David J. Adams

    (Wellcome Trust Sanger Institute)

  • Wolfgang J. Weninger

    (Center for Anatomy & Cell Biology, Medical University of Vienna)

  • Timothy Mohun

    (The Francis Crick Institute)

  • Myriam Hemberger

    (The Babraham Institute, Babraham Research Campus
    Centre for Trophoblast Research, University of Cambridge)

Abstract

Large-scale phenotyping efforts have demonstrated that approximately 25–30% of mouse gene knockouts cause intrauterine lethality. Analysis of these mutants has largely focused on the embryo and not the placenta, despite the crucial role of this extraembryonic organ for developmental progression. Here we screened 103 embryonic lethal and sub-viable mouse knockout lines from the Deciphering the Mechanisms of Developmental Disorders program for placental phenotypes. We found that 68% of knockout lines that are lethal at or after mid-gestation exhibited placental dysmorphologies. Early lethality (embryonic days 9.5–14.5) is almost always associated with severe placental malformations. Placental defects correlate strongly with abnormal brain, heart and vascular development. Analysis of mutant trophoblast stem cells and conditional knockouts suggests that a considerable number of factors that cause embryonic lethality when ablated have primary gene function in trophoblast cells. Our data highlight the hugely under-appreciated importance of placental defects in contributing to abnormal embryo development and suggest key molecular nodes that govern placenta formation.

Suggested Citation

  • Vicente Perez-Garcia & Elena Fineberg & Robert Wilson & Alexander Murray & Cecilia Icoresi Mazzeo & Catherine Tudor & Arnold Sienerth & Jacqueline K. White & Elizabeth Tuck & Edward J. Ryder & Diane G, 2018. "Placentation defects are highly prevalent in embryonic lethal mouse mutants," Nature, Nature, vol. 555(7697), pages 463-468, March.
  • Handle: RePEc:nat:nature:v:555:y:2018:i:7697:d:10.1038_nature26002
    DOI: 10.1038/nature26002
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    Citations

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    Cited by:

    1. Chen Dong & Shuhua Fu & Rowan M. Karvas & Brian Chew & Laura A. Fischer & Xiaoyun Xing & Jessica K. Harrison & Pooja Popli & Ramakrishna Kommagani & Ting Wang & Bo Zhang & Thorold W. Theunissen, 2022. "A genome-wide CRISPR-Cas9 knockout screen identifies essential and growth-restricting genes in human trophoblast stem cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Simon Andrews & Christel Krueger & Maravillas Mellado-Lopez & Myriam Hemberger & Wendy Dean & Vicente Perez-Garcia & Courtney W. Hanna, 2023. "Mechanisms and function of de novo DNA methylation in placental development reveals an essential role for DNMT3B," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Bethany N. Radford & Xiang Zhao & Tali Glazer & Malcolm Eaton & Danielle Blackwell & Shuhiba Mohammad & Lucas Daniel Lo Vercio & Jay Devine & Tali Shalom-Barak & Benedikt Hallgrimsson & James C. Cross, 2023. "Defects in placental syncytiotrophoblast cells are a common cause of developmental heart disease," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Jong Geol Lee & Jung-Min Yon & Globinna Kim & Seul-Gi Lee & C-Yoon Kim & Seung-A Cheong & Hyun-Yi Kim & Jiyoung Yu & Kyunggon Kim & Young Hoon Sung & Hyun Ju Yoo & Dong-Cheol Woo & Jin Kyung Rho & Cha, 2024. "PIBF1 regulates trophoblast syncytialization and promotes cardiovascular development," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    5. Shilei Bi & Lijun Huang & Yongjie Chen & Zhenhua Hu & Shanze Li & Yifan Wang & Baoying Huang & Lizi Zhang & Yuanyuan Huang & Beibei Dai & Lili Du & Zhaowei Tu & Yijing Wang & Dan Xu & Xiaotong Xu & We, 2024. "KAT8-mediated H4K16ac is essential for sustaining trophoblast self-renewal and proliferation via regulating CDX2," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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