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Nodal signaling establishes a competency window for stochastic cell fate switching

Specification of the germ layers by Nodal signaling has long been regarded as an archetype of how graded morphogens induce different cell fates. However, this deterministic model cannot explain why only a subset of cells at the early zebrafish embryo margin adopt the endodermal fate, whereas their i...

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Autores principales: Economou, Andrew D., Guglielmi, Luca, East, Philip, Hill, Caroline S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615190/
https://www.ncbi.nlm.nih.gov/pubmed/36473458
http://dx.doi.org/10.1016/j.devcel.2022.11.008
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author Economou, Andrew D.
Guglielmi, Luca
East, Philip
Hill, Caroline S.
author_facet Economou, Andrew D.
Guglielmi, Luca
East, Philip
Hill, Caroline S.
author_sort Economou, Andrew D.
collection PubMed
description Specification of the germ layers by Nodal signaling has long been regarded as an archetype of how graded morphogens induce different cell fates. However, this deterministic model cannot explain why only a subset of cells at the early zebrafish embryo margin adopt the endodermal fate, whereas their immediate neighbours, experiencing a similar signaling environment, become mesoderm. Combining pharmacology, quantitative imaging and single cell transcriptomics, we demonstrate that sustained Nodal signaling establishes a bipotential progenitor state from which cells can switch to an endodermal fate or differentiate into mesoderm. Switching is a random event, the likelihood of which is modulated by Fgf signaling. This inherently imprecise mechanism nevertheless leads to robust endoderm formation because of buffering at later stages. Thus, in contrast to previous deterministic models of morphogen action, Nodal signaling establishes a temporal window when cells are competent to undergo a stochastic cell fate switch, rather than determining fate itself.
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spelling pubmed-76151902023-10-26 Nodal signaling establishes a competency window for stochastic cell fate switching Economou, Andrew D. Guglielmi, Luca East, Philip Hill, Caroline S. Dev Cell Article Specification of the germ layers by Nodal signaling has long been regarded as an archetype of how graded morphogens induce different cell fates. However, this deterministic model cannot explain why only a subset of cells at the early zebrafish embryo margin adopt the endodermal fate, whereas their immediate neighbours, experiencing a similar signaling environment, become mesoderm. Combining pharmacology, quantitative imaging and single cell transcriptomics, we demonstrate that sustained Nodal signaling establishes a bipotential progenitor state from which cells can switch to an endodermal fate or differentiate into mesoderm. Switching is a random event, the likelihood of which is modulated by Fgf signaling. This inherently imprecise mechanism nevertheless leads to robust endoderm formation because of buffering at later stages. Thus, in contrast to previous deterministic models of morphogen action, Nodal signaling establishes a temporal window when cells are competent to undergo a stochastic cell fate switch, rather than determining fate itself. 2022-12-05 /pmc/articles/PMC7615190/ /pubmed/36473458 http://dx.doi.org/10.1016/j.devcel.2022.11.008 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a BY 4.0 (https://creativecommons.org/licenses/by/4.0/) International license. https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Economou, Andrew D.
Guglielmi, Luca
East, Philip
Hill, Caroline S.
Nodal signaling establishes a competency window for stochastic cell fate switching
title Nodal signaling establishes a competency window for stochastic cell fate switching
title_full Nodal signaling establishes a competency window for stochastic cell fate switching
title_fullStr Nodal signaling establishes a competency window for stochastic cell fate switching
title_full_unstemmed Nodal signaling establishes a competency window for stochastic cell fate switching
title_short Nodal signaling establishes a competency window for stochastic cell fate switching
title_sort nodal signaling establishes a competency window for stochastic cell fate switching
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615190/
https://www.ncbi.nlm.nih.gov/pubmed/36473458
http://dx.doi.org/10.1016/j.devcel.2022.11.008
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