{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:54:03Z","timestamp":1785412443287,"version":"3.56.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"30","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,7,28]]},"abstract":"<jats:p>\n                    During development, cells gradually assume specialized fates via changes of transcriptional dynamics in thousands of genes. Landscape modeling approaches, which abstract from the underlying gene regulatory networks and reason in a low-dimensional phenotypic space, have been remarkably successful in explaining terminal fate outcomes. The success of these models also prompts their application toward inferring dynamic perturbations of multicellular patterning that alter cell fate outcomes in predictable ways, a task that is otherwise highly challenging due to the complex dynamics of the underlying gene circuits. Here, we accomplish this task by combining a landscape model for\n                    <jats:italic toggle=\"yes\">Caenorhabditis elegans<\/jats:italic>\n                    vulval fate patterning with temporally controlled perturbations of EGF and Notch signaling in vivo using temperature-sensitive mutant alleles. We find that nonintuitive fate outcomes that emerge in combinations of these alleles at static temperature conditions through pathway epistasis are correctly predicted by the model. We then show that short pulses of signaling in these genetic backgrounds, delivered via temperature shifts, can be used to guide both the fraction of induced precursor cells and the specific fates they adopt with quantitative precision. Analysis of the underlying cellular landscapes indicates that cell fate guidance via pulses of signaling effectively redesigns the decision structure into one that has no equivalent in normal development, namely, a conversion of the three-way cell fate decision topology into two sequential binary fate decisions. Our results highlight the predictive power of landscape models and illustrate a method to quantitatively guide cell fate acquisition in a developmental context.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2521973123","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T19:15:07Z","timestamp":1784574907000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Quantitative guiding of developmental cell fate patterns using a dynamical landscape model"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9277-4457","authenticated-orcid":false,"given":"Ismail","family":"Hajji","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013cjyk83","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratoire de Physique des Cellules et Cancers, Institut Curie, CNRS UMR168, Universit\u00e9 Paris Science et Lettres","place":["Paris PARIS CEDEX, France"]},{"name":"Institut Pierre-Gilles de Gennes","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7230-137X","authenticated-orcid":false,"given":"Francis","family":"Corson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratoire de Physique de l\u2019Ecole Normale Sup\u00e9rieure, CNRS UMR8023, Universit\u00e9 Paris Sciences et Lettres, Sorbonne Universit\u00e9, Universit\u00e9 Paris Cit\u00e9","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8176-8585","authenticated-orcid":false,"given":"Wolfgang","family":"Keil","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013cjyk83","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratoire de Physique des Cellules et Cancers, Institut Curie, CNRS UMR168, Universit\u00e9 Paris 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Paluch Cell shape noise strength regulates the rate of shape change during EMT-associated cell spreading. bioXriv [Preprint] (2024). https:\/\/doi.org\/10.1101\/2024.10.14.618199 (Accessed 24 April 2026).","DOI":"10.1101\/2024.10.14.618199"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2521973123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T19:16:06Z","timestamp":1784574966000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2521973123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":46,"journal-issue":{"issue":"30","published-print":{"date-parts":[[2026,7,28]]}},"alternative-id":["10.1073\/pnas.2521973123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2521973123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]},"assertion":[{"value":"2025-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2521973123"}}