Growth factor-mediated coupling between lineage size and cell fate choice underlies robustness of mammalian development
Jeremy P Herder,
Posted 27 Dec 2019
bioRxiv DOI: 10.1101/2019.12.27.889006 (published DOI: 10.7554/eLife.56079)
Posted 27 Dec 2019
Precise control and maintenance of the size of cell populations is fundamental for organismal development and homeostasis. The three cell types that comprise the mammalian blastocyst-stage embryo are generated in precise proportions and over a short time, suggesting a size control mechanism ensures a reproducible outcome. Guided by experimental observations, we developed a minimal mathematical model that shows growth factor signaling is sufficient to guarantee this robustness. The model anticipates, without additional parameter fitting, the response of the embryo to perturbations in its lineage composition. We experimentally added lineage-restricted cells to the epiblast both in vivo and in silico , which resulted in a shift of the fate of progenitors away from the supernumerary cell type, while eliminating cells using laser ablation biased the specification of progenitors towards the targeted cell type. Finally, we show that FGF4 couples cell fate decisions to lineage composition through changes in local concentration of the growth factor. Our results provide a basis for the regulative abilities of the mammalian embryo and reveal how, in a self-organizing system, individual cell fate decisions are coordinated at the population level to robustly generate tissues in the right proportions.
- Downloaded 1,433 times
- Download rankings, all-time:
- Site-wide: 7,142 out of 100,699
- In developmental biology: 135 out of 3,007
- Year to date:
- Site-wide: 2,368 out of 100,699
- Since beginning of last month:
- Site-wide: 19,146 out of 100,699
Downloads over time
Distribution of downloads per paper, site-wide
- 20 Oct 2020: Support for sorting preprints using Twitter activity has been removed, at least temporarily, until a new source of social media activity data becomes available.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!