Abstract

The Notch signalling pathway plays fundamental roles in diverse developmental processes in metazoans, where it is important in driving cell fate and directing differentiation of various cell types. However, we still have limited knowledge about the role of Notch in early preimplantation stages of mammalian development, or how it interacts with other signalling pathways active at these stages such as Hippo. By using genetic and pharmacological tools in vivo, together with image analysis of single embryos and pluripotent cell culture, we have found that Notch is active from the 4-cell stage. Transcriptomic analysis in single morula identified novel Notch targets, such as early naïve pluripotency markers or transcriptional repressors such as TLE4. Our results reveal a previously undescribed role for Notch in driving transitions during the gradual loss of potency that takes place in the early mouse embryo prior to the first lineage decisions.

Data availability

Sequencing data have been deposited in GEO under accession code GSE121979.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Sergio Menchero

    Department of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4592-7259
  2. Isabel Rollan

    Department of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  3. Antonio Lopez-Izquierdo

    Department of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  4. Maria Jose Andreu

    Department of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  5. Julio Sainz de Aja

    Department of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  6. Minjung Kang

    Developmental Biology Program, Sloan Kettering Institute, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Javier Adan

    Department of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  8. Rui Benedito

    Department of Molecular Genetics of Angiogenesis, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  9. Teresa Rayon

    Department of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  10. Anna-Katerina Hadjantonakis

    Developmental Biology Program, Sloan Kettering Institute, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7580-5124
  11. Miguel Manzanares

    Department of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
    For correspondence
    mmanzanares@cnic.es
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4849-2836

Funding

Ministerio de Economía y Competitividad (BFU2017-84914-P)

  • Sergio Menchero
  • Isabel Rollan
  • Antonio Lopez-Izquierdo
  • Maria Jose Andreu
  • Julio Sainz de Aja
  • Javier Adan
  • Teresa Rayon
  • Miguel Manzanares

ProCNIC Foundation

  • Sergio Menchero
  • Isabel Rollan
  • Antonio Lopez-Izquierdo
  • Maria Jose Andreu
  • Julio Sainz de Aja
  • Javier Adan
  • Rui Benedito
  • Teresa Rayon
  • Miguel Manzanares

National Institutes of Health (NIH-R01DK084391)

  • Minjung Kang
  • Anna-Katerina Hadjantonakis

Ministerio de Economía y Competitividad (BFU2015-72319-EXP)

  • Sergio Menchero
  • Isabel Rollan
  • Maria Jose Andreu
  • Miguel Manzanares

Ministerio de Economía y Competitividad (SEV-2015-0505)

  • Sergio Menchero
  • Isabel Rollan
  • Antonio Lopez-Izquierdo
  • Maria Jose Andreu
  • Julio Sainz de Aja
  • Javier Adan
  • Rui Benedito
  • Teresa Rayon
  • Miguel Manzanares

Ministerio de Economía y Competitividad (SVP-2013-067930)

  • Sergio Menchero

National Institutes of Health (NIH-R01HD094868)

  • Minjung Kang
  • Anna-Katerina Hadjantonakis

National Institutes of Health (NIH-P30CA008748)

  • Minjung Kang
  • Anna-Katerina Hadjantonakis

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

Reviewing Editor

  1. Elizabeth Robertson, University of Oxford, United Kingdom

Ethics

Animal experimentation: This study was performed in strict accordance with national and European Legislation. Procedures were approved by the CNIC Animal Welfare Ethics Committee and by the Area of Animal Protection of the Regional Government of Madrid (ref. PROEX 196/14).

Version history

  1. Received: October 17, 2018
  2. Accepted: April 7, 2019
  3. Accepted Manuscript published: April 8, 2019 (version 1)
  4. Version of Record published: April 26, 2019 (version 2)

Copyright

© 2019, Menchero 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. Sergio Menchero
  2. Isabel Rollan
  3. Antonio Lopez-Izquierdo
  4. Maria Jose Andreu
  5. Julio Sainz de Aja
  6. Minjung Kang
  7. Javier Adan
  8. Rui Benedito
  9. Teresa Rayon
  10. Anna-Katerina Hadjantonakis
  11. Miguel Manzanares
(2019)
Transitions in cell potency during early mouse development are driven by Notch
eLife 8:e42930.
https://doi.org/10.7554/eLife.42930

Share this article

https://doi.org/10.7554/eLife.42930

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