{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T02:04:07Z","timestamp":1778637847396,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1009040","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T00:00:00Z","timestamp":1623196800000}}],"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"crossref","award":["E-26 010.001877\/2015"],"award-info":[{"award-number":["E-26 010.001877\/2015"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"crossref","award":["E-26 010.001877\/2015"],"award-info":[{"award-number":["E-26 010.001877\/2015"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"crossref","award":["E-26 010.001877\/2015"],"award-info":[{"award-number":["E-26 010.001877\/2015"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CAPES and CNPq","award":["PhD and Pos-Doc fellowship"],"award-info":[{"award-number":["PhD and Pos-Doc fellowship"]}]},{"name":"CAPES and CNPq","award":["PhD and Pos-Doc fellowship"],"award-info":[{"award-number":["PhD and Pos-Doc fellowship"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Dorsal-ventral patterning of the\n                    <jats:italic>Drosophila<\/jats:italic>\n                    embryo depends on the NF\u03baB superfamily transcription factor Dorsal (Dl). Toll receptor activation signals for degradation of the I\u03baB inhibitor Cactus (Cact), leading to a ventral-to-dorsal nuclear Dl gradient. Cact is critical for Dl nuclear import, as it binds to and prevents Dl from entering the nuclei. Quantitative analysis of\n                    <jats:italic>cact<\/jats:italic>\n                    mutants revealed an additional Cact function to promote Dl nuclear translocation in ventral regions of the embryo. To investigate this dual Cact role, we developed a predictive model based on a reaction-diffusion regulatory network. This network distinguishes non-uniform Toll-dependent Dl nuclear import and Cact degradation, from the Toll-independent processes of Cact degradation and reversible nuclear-cytoplasmic Dl flow. In addition, it incorporates translational control of Cact levels by Dl. Our model successfully reproduces wild-type data and emulates the Dl nuclear gradient in mutant\n                    <jats:italic>dl<\/jats:italic>\n                    and\n                    <jats:italic>cact<\/jats:italic>\n                    allelic combinations. Our results indicate that the dual role of Cact depends on the dynamics of Dl-Cact trimers along the dorsal-ventral axis: In the absence of Toll activation, free Dl-Cact trimers retain Dl in the cytoplasm, limiting the flow of Dl into the nucleus; in ventral-lateral regions, Dl-Cact trimers are recruited by Toll activation into predominant signaling complexes and promote Dl nuclear translocation. Simulations suggest that the balance between Toll-dependent and Toll-independent processes are key to this dynamics and reproduce the full assortment of Cact effects. Considering the high evolutionary conservation of these pathways, our analysis should contribute to understanding NF\u03baB\/c-Rel activation in other contexts such as in the vertebrate immune system and disease.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1009040","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T15:54:12Z","timestamp":1622130852000},"page":"e1009040","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["A reaction-diffusion network model predicts a dual role of Cactus\/I\u03baB to regulate Dorsal\/NF\u03baB nuclear translocation in Drosophila"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7216-4376","authenticated-orcid":true,"given":"Claudio D. 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