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dc.contributor.authorGrant, Paul K.
dc.contributor.authorSzep, Gregory
dc.contributor.authorPatange, Om
dc.contributor.authorHalatek, Jacob
dc.contributor.authorCoppard, Valerie
dc.contributor.authorCsikász-Nagy, Attila
dc.contributor.authorHaseloff, Jim
dc.contributor.authorLocke, James C. W.
dc.contributor.authorDalchau, Neil
dc.contributor.authorPhillips, Andrew
dc.date.accessioned2020-11-02T16:14:59Z
dc.date.available2020-11-02T16:14:59Z
dc.date.issued2020-11-02
dc.date.submitted2020-07-15
dc.identifier.others41467-020-19098-w
dc.identifier.other19098
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/312327
dc.description.abstractAbstract: During development, cells gain positional information through the interpretation of dynamic morphogen gradients. A proposed mechanism for interpreting opposing morphogen gradients is mutual inhibition of downstream transcription factors, but isolating the role of this specific motif within a natural network remains a challenge. Here, we engineer a synthetic morphogen-induced mutual inhibition circuit in E. coli populations and show that mutual inhibition alone is sufficient to produce stable domains of gene expression in response to dynamic morphogen gradients, provided the spatial average of the morphogens falls within the region of bistability at the single cell level. When we add sender devices, the resulting patterning circuit produces theoretically predicted self-organised gene expression domains in response to a single gradient. We develop computational models of our synthetic circuits parameterised to timecourse fluorescence data, providing both a theoretical and experimental framework for engineering morphogen-induced spatial patterning in cell populations.
dc.languageen
dc.publisherNature Publishing Group UK
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectArticle
dc.subject/631/114/2114
dc.subject/631/136/756
dc.subject/631/553/552
dc.subject/38/35
dc.subject/38/62
dc.subject/14/63
dc.subjectarticle
dc.titleInterpretation of morphogen gradients by a synthetic bistable circuit
dc.typeArticle
dc.date.updated2020-11-02T16:14:51Z
prism.issueIdentifier1
prism.publicationNameNature Communications
prism.volume11
dc.identifier.doi10.17863/CAM.59419
dcterms.dateAccepted2020-09-23
rioxxterms.versionofrecord10.1038/s41467-020-19098-w
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidGrant, Paul K. [0000-0002-1099-0461]
dc.contributor.orcidSzep, Gregory [0000-0001-7680-8178]
dc.contributor.orcidPatange, Om [0000-0002-2810-6216]
dc.contributor.orcidHalatek, Jacob [0000-0003-3211-2253]
dc.contributor.orcidCsikász-Nagy, Attila [0000-0002-2919-5601]
dc.contributor.orcidHaseloff, Jim [0000-0003-4793-8058]
dc.contributor.orcidDalchau, Neil [0000-0002-4872-6914]
dc.contributor.orcidPhillips, Andrew [0000-0001-9725-1073]
dc.identifier.eissn2041-1723


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)