{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T01:09:53Z","timestamp":1773364193970,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1010306","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000}}],"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T00:00:00Z","timestamp":1658361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["PHY-2019745"],"award-info":[{"award-number":["PHY-2019745"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["PHY 1522550"],"award-info":[{"award-number":["PHY 1522550"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CHEM-1614101"],"award-info":[{"award-number":["CHEM-1614101"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["GRFP no. 1842494"],"award-info":[{"award-number":["GRFP no. 1842494"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000893","name":"Simons Foundation","doi-asserted-by":"publisher","award":["594598, QN"],"award-info":[{"award-number":["594598, QN"]}],"id":[{"id":"10.13039\/100000893","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>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\u201d 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\u2013shot and white\u2013for 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 \u201cproofreading\u201d 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.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1010306","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T18:01:33Z","timestamp":1658426493000},"page":"e1010306","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Stochastic fluctuations promote ordered pattern formation of cells in the Notch-Delta signaling pathway"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1735-0747","authenticated-orcid":true,"given":"Madeline","family":"Galbraith","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4302-9906","authenticated-orcid":true,"given":"Federico","family":"Bocci","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9448-0388","authenticated-orcid":true,"given":"Jos\u00e9 N.","family":"Onuchic","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,7,21]]},"reference":[{"issue":"2","key":"pcbi.1010306.ref001","first-page":"151","article-title":"Notch: a key regulator of tumor angiogenesis and metastasis","volume":"27","author":"A Garcia","year":"2012","journal-title":"Histol Histopathol"},{"issue":"23","key":"pcbi.1010306.ref002","doi-asserted-by":"crossref","first-page":"4297","DOI":"10.1242\/dev.080515","article-title":"Drosophila neuroblasts: a model for stem cell biology","volume":"139","author":"CCF Homem","year":"2012","journal-title":"Development"},{"key":"pcbi.1010306.ref003","first-page":"9","article-title":"Notch Signaling in Embryology and Cancer, Notch Signaling in Embryology","volume":"1218","author":"J Reichrath","year":"2020","journal-title":"Adv Exp Med Biol"},{"issue":"17","key":"pcbi.1010306.ref004","doi-asserted-by":"crossref","first-page":"3241","DOI":"10.1242\/dev.124.17.3241","article-title":"Feed-back mechanisms affecting Notch activation at the dorsoventral boundary in the Drosophila wing","volume":"124","author":"JFC de","year":"1997","journal-title":"Development"},{"issue":"1","key":"pcbi.1010306.ref005","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ydbio.2019.06.024","article-title":"What are you synching about? 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