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Stochastic fluctuations promote ordered pattern formation of cells in the Notch-Delta signaling pathway

The Notch-Delta signaling pathway mediates cell differentiation implicated in many regulatory processes including spatiotemporal patterning in tissues by promoting alternate cell fates between neighboring cells. At the multicellular level, this "lateral inhibition” principle leads to checkerboa...

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Autores principales: Galbraith, Madeline, Bocci, Federico, Onuchic, José N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345490/
https://www.ncbi.nlm.nih.gov/pubmed/35862460
http://dx.doi.org/10.1371/journal.pcbi.1010306
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author Galbraith, Madeline
Bocci, Federico
Onuchic, José N.
author_facet Galbraith, Madeline
Bocci, Federico
Onuchic, José N.
author_sort Galbraith, Madeline
collection PubMed
description The Notch-Delta signaling pathway mediates cell differentiation implicated in many regulatory processes including spatiotemporal patterning in tissues by promoting alternate cell fates between neighboring cells. At the multicellular level, this "lateral inhibition” principle leads to checkerboard patterns with alternation of Sender and Receiver cells. While it is well known that stochasticity modulates cell fate specification, little is known about how stochastic fluctuations at the cellular level propagate during multicell pattern formation. Here, we model stochastic fluctuations in the Notch-Delta pathway in the presence of two different noise types–shot and white–for a multicell system. Our results show that intermediate fluctuations reduce disorder and guide the multicell lattice toward checkerboard-like patterns. By further analyzing cell fate transition events, we demonstrate that intermediate noise amplitudes provide enough perturbation to facilitate “proofreading” of disordered patterns and cause cells to switch to the correct ordered state (Sender surrounded by Receivers, and vice versa). Conversely, high noise can override environmental signals coming from neighboring cells and lead to switching between ordered and disordered patterns. Therefore, in analogy with spin glass systems, intermediate noise levels allow the multicell Notch system to escape frustrated patterns and relax towards the lower energy checkerboard pattern while at large noise levels the system is unable to find this ordered base of attraction.
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spelling pubmed-93454902022-08-03 Stochastic fluctuations promote ordered pattern formation of cells in the Notch-Delta signaling pathway Galbraith, Madeline Bocci, Federico Onuchic, José N. PLoS Comput Biol Research Article The Notch-Delta signaling pathway mediates cell differentiation implicated in many regulatory processes including spatiotemporal patterning in tissues by promoting alternate cell fates between neighboring cells. At the multicellular level, this "lateral inhibition” principle leads to checkerboard patterns with alternation of Sender and Receiver cells. While it is well known that stochasticity modulates cell fate specification, little is known about how stochastic fluctuations at the cellular level propagate during multicell pattern formation. Here, we model stochastic fluctuations in the Notch-Delta pathway in the presence of two different noise types–shot and white–for a multicell system. Our results show that intermediate fluctuations reduce disorder and guide the multicell lattice toward checkerboard-like patterns. By further analyzing cell fate transition events, we demonstrate that intermediate noise amplitudes provide enough perturbation to facilitate “proofreading” of disordered patterns and cause cells to switch to the correct ordered state (Sender surrounded by Receivers, and vice versa). Conversely, high noise can override environmental signals coming from neighboring cells and lead to switching between ordered and disordered patterns. Therefore, in analogy with spin glass systems, intermediate noise levels allow the multicell Notch system to escape frustrated patterns and relax towards the lower energy checkerboard pattern while at large noise levels the system is unable to find this ordered base of attraction. Public Library of Science 2022-07-21 /pmc/articles/PMC9345490/ /pubmed/35862460 http://dx.doi.org/10.1371/journal.pcbi.1010306 Text en © 2022 Galbraith et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Galbraith, Madeline
Bocci, Federico
Onuchic, José N.
Stochastic fluctuations promote ordered pattern formation of cells in the Notch-Delta signaling pathway
title Stochastic fluctuations promote ordered pattern formation of cells in the Notch-Delta signaling pathway
title_full Stochastic fluctuations promote ordered pattern formation of cells in the Notch-Delta signaling pathway
title_fullStr Stochastic fluctuations promote ordered pattern formation of cells in the Notch-Delta signaling pathway
title_full_unstemmed Stochastic fluctuations promote ordered pattern formation of cells in the Notch-Delta signaling pathway
title_short Stochastic fluctuations promote ordered pattern formation of cells in the Notch-Delta signaling pathway
title_sort stochastic fluctuations promote ordered pattern formation of cells in the notch-delta signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345490/
https://www.ncbi.nlm.nih.gov/pubmed/35862460
http://dx.doi.org/10.1371/journal.pcbi.1010306
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