Growth factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development
- Memorial Sloan Kettering Cancer Center, United States
- Universitat Pompeu Fabra, Spain
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.
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Asynchronous fate decisions by single cells collectively ensure consistent lineage composition in the mouse blastocyst.http://github.com/nestorsaiz/saiz-et-al_2016.
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A Sprouty4 reporter to monitor FGF/ERK signaling activity in ESCs and mice.https://doi.org/10.6084/m9.figshare.c.4142081.
Article and author information
Author details
Jordi Garcia-Ojalvo
Anna-Katerina Hadjantonakis
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).
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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Growth factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development
eLife 9:e56079.
https://doi.org/10.7554/eLife.56079
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