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Combinatorial interpretation of BMP and WNT allows BMP to act as a morphogen in time but not in concentration

Elena Camacho-Aguilar, Sumin Yoon, Miguel A. Ortiz-Salazar, View ORCID ProfileAryeh Warmflash
doi: https://doi.org/10.1101/2022.11.11.516212
Elena Camacho-Aguilar
1Department of Biosciences, Rice University, Houston TX 77005
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Sumin Yoon
1Department of Biosciences, Rice University, Houston TX 77005
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Miguel A. Ortiz-Salazar
1Department of Biosciences, Rice University, Houston TX 77005
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Aryeh Warmflash
1Department of Biosciences, Rice University, Houston TX 77005
2Department of Bioengineering, Rice University, Houston TX 77005
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  • ORCID record for Aryeh Warmflash
  • For correspondence: aryeh.warmflash@rice.edu
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Abstract

Secreted morphogen signals play a key role in the determination of cell fates during embryonic development. BMP signaling is essential for vertebrate gastrulation, as it initiates a cascade of signals that controls the self-organized patterning of the three germ layers. Although morphogen signals are typically thought to induce cell fates in a concentration-dependent manner, development is a highly dynamic process, so it is crucial to understand how time-dependent signaling affects cellular differentiation. Here we show that varying the duration of BMP signaling leads to either pluripotent, mesodermal, and extraembryonic states, while varying the concentration does not cause efficient mesodermal differentiation at any dose. Thus, there is a morphogen effect in time but not in concentration, and an appropriately timed pulse of BMP induces hPSCs to a mesodermal fate more efficiently that sustained signaling at any concentration. Using live cell imaging of signaling and cell fate reporters together with a simple mathematical model, we show that this effect is due to a combinatorial interpretation of the applied BMP signal and induced endogenous WNT signaling. Our findings have implications for how signaling pathways control the landscape of early human development.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted November 12, 2022.
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Combinatorial interpretation of BMP and WNT allows BMP to act as a morphogen in time but not in concentration
Elena Camacho-Aguilar, Sumin Yoon, Miguel A. Ortiz-Salazar, Aryeh Warmflash
bioRxiv 2022.11.11.516212; doi: https://doi.org/10.1101/2022.11.11.516212
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Combinatorial interpretation of BMP and WNT allows BMP to act as a morphogen in time but not in concentration
Elena Camacho-Aguilar, Sumin Yoon, Miguel A. Ortiz-Salazar, Aryeh Warmflash
bioRxiv 2022.11.11.516212; doi: https://doi.org/10.1101/2022.11.11.516212

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