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

dc.citation.articleNumbere1010306en_US
dc.citation.issueNumber7en_US
dc.citation.journalTitlePLOS Computational Biologyen_US
dc.citation.volumeNumber18en_US
dc.contributor.authorGalbraith, Madelineen_US
dc.contributor.authorBocci, Federicoen_US
dc.contributor.authorOnuchic, José N.en_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.date.accessioned2022-09-01T14:18:22Zen_US
dc.date.available2022-09-01T14:18:22Zen_US
dc.date.issued2022en_US
dc.description.abstractThe 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.en_US
dc.identifier.citationGalbraith, Madeline, Bocci, Federico and Onuchic, José N.. "Stochastic fluctuations promote ordered pattern formation of cells in the Notch-Delta signaling pathway." <i>PLOS Computational Biology,</i> 18, no. 7 (2022) Public Library of Science: https://doi.org/10.1371/journal.pcbi.1010306.en_US
dc.identifier.digitaljournal-pcbi-1010306en_US
dc.identifier.doihttps://doi.org/10.1371/journal.pcbi.1010306en_US
dc.identifier.urihttps://hdl.handle.net/1911/113168en_US
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleStochastic fluctuations promote ordered pattern formation of cells in the Notch-Delta signaling pathwayen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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