1. Developmental Biology
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Growth factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development

  1. Nestor Saiz  Is a corresponding author
  2. Laura Mora-Bitria
  3. Shahadat Rahman
  4. Hannah George
  5. Jeremy Herder
  6. Jordi Garcia-Ojalvo  Is a corresponding author
  7. Anna-Katerina Hadjantonakis  Is a corresponding author
  1. Memorial Sloan Kettering Cancer Center, United States
  2. Universitat Pompeu Fabra, Spain
Research Article
  • Cited 5
  • Views 2,699
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Cite this article as: eLife 2020;9:e56079 doi: 10.7554/eLife.56079
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Abstract

Precise control and maintenance of population size is fundamental for organismal development and homeostasis. The three cell types of the mammalian blastocyst are generated in precise proportions over a short time, suggesting a mechanism to ensure a reproducible outcome. We developed a minimal mathematical model demonstrating growth factor signaling is sufficient to guarantee this robustness and which anticipates an embryo's response to perturbations in lineage composition. Addition of lineage-restricted cells both in vivo and in silico, causes a shift of the fate of progenitors away from the supernumerary cell type, while eliminating cells using laser ablation biases the specification of progenitors towards the targeted cell type. Finally, FGF4 couples fate decisions to lineage composition through changes in local growth factor concentration, providing a basis for the regulative abilities of the early mammalian embryo whereby fate decisions are coordinated at the population level to robustly generate tissues in the right proportions.

Data availability

All image data processing was done in R version 3.4.2, using RStudio as an interactive development environment. All processed data as well as the code used to transform data and classify cells is available at https://github.com/nestorsaiz/saiz-et-al_2020 and upon request.All raw confocal images and data tables will be freely available on Figshare with DOI 10.6084/m9.figshare.c.4736507.Code for phase-plane analysis and modeling is available at https://github.com/jgojalvo/EmbryoRobustness.

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

Article and author information

Author details

  1. Nestor Saiz

    Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States
    For correspondence
    saizaren@mskcc.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0637-791X
  2. Laura Mora-Bitria

    Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  3. Shahadat Rahman

    Developmental Biology, Memorial Sloan Kettering Cancer Center, 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:" 0000-0002-3424-6768
  4. Hannah George

    Developmental Biology, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jeremy Herder

    Developmental Biology, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jordi Garcia-Ojalvo

    Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
    For correspondence
    jordi.g.ojalvo@upf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3716-7520
  7. Anna-Katerina Hadjantonakis

    Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States
    For correspondence
    hadj@mskcc.org
    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

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01-HD094868)

  • Anna-Katerina Hadjantonakis

National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK084391)

  • Anna-Katerina Hadjantonakis

National Cancer Institute (P30-CA008748)

  • Anna-Katerina Hadjantonakis

Spanish Ministry of Science, Innovation and Universities (PGC2018-101251-B-I00)

  • Jordi Garcia-Ojalvo

Spanish Ministry of Science, Innovation and Universities (CEX2018-000792-M)

  • Jordi Garcia-Ojalvo

ICREA

  • Jordi Garcia-Ojalvo

STARR Foundation Tri-Institutional Stem Cell Postdoctoral fellowship

  • Nestor Saiz

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

Ethics

Animal experimentation: All animal work was approved by Memorial Sloan Kettering Cancer Center's Institutional Animal Care and Use Committee (Protocol 03-12-017, Hadjantonakis PI).

Reviewing Editor

  1. Elizabeth Robertson, University of Oxford, United Kingdom

Publication history

  1. Received: February 16, 2020
  2. Accepted: July 24, 2020
  3. Accepted Manuscript published: July 28, 2020 (version 1)
  4. Version of Record published: September 18, 2020 (version 2)
  5. Version of Record updated: October 13, 2020 (version 3)

Copyright

© 2020, Saiz 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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