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Zfhx3-mediated genetic ablation of the SCN abolishes light entrainable circadian activity while sparing food anticipatory activity.

cam.depositDate2021-12-02
cam.issuedOnline2021-09-16
dc.contributor.authorWilcox, Ashleigh G
dc.contributor.authorBains, R Sonia
dc.contributor.authorWilliams, Debbie
dc.contributor.authorJoynson, Elizabeth
dc.contributor.authorVizor, Lucie
dc.contributor.authorOliver, Peter L
dc.contributor.authorMaywood, Elizabeth S
dc.contributor.authorHastings, Michael H
dc.contributor.authorBanks, Gareth
dc.contributor.authorNolan, Patrick M
dc.contributor.orcidHastings, Michael [0000-0001-8576-6651]
dc.date.accessioned2021-12-03T00:30:33Z
dc.date.available2021-12-03T00:30:33Z
dc.date.issued2021-10-22
dc.date.updated2021-12-02T10:00:19Z
dc.description.abstractCircadian rhythms persist in almost all organisms and are crucial for maintaining appropriate timing in physiology and behaviour. Here, we describe a mouse mutant where the central mammalian pacemaker, the suprachiasmatic nucleus (SCN), has been genetically ablated by conditional deletion of the transcription factor Zfhx3 in the developing hypothalamus. Mutants were arrhythmic over the light-dark cycle and in constant darkness. Moreover, rhythms of metabolic parameters were ablated in vivo although molecular oscillations in the liver maintained some rhythmicity. Despite disruptions to SCN cell identity and circuitry, mutants could still anticipate food availability, yet other zeitgebers - including social cues from cage-mates - were ineffective in restoring rhythmicity although activity levels in mutants were altered. This work highlights a critical role for Zfhx3 in the development of a functional SCN, while its genetic ablation further defines the contribution of SCN circuitry in orchestrating physiological and behavioral responses to environmental signals.
dc.format.mediumElectronic-eCollection
dc.identifier.doi10.17863/CAM.78667
dc.identifier.eissn2589-0042
dc.identifier.issn2589-0042
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331222
dc.language.isoeng
dc.publisherElsevier BV
dc.publisher.departmentMrc Laboratory of Molecular Biology
dc.publisher.urlhttp://dx.doi.org/10.1016/j.isci.2021.103142
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectBiological sciences
dc.subjectMolecular biology
dc.subjectNeuroscience
dc.subjectPhysiology
dc.titleZfhx3-mediated genetic ablation of the SCN abolishes light entrainable circadian activity while sparing food anticipatory activity.
dc.typeArticle
dcterms.dateAccepted2021-09-14
prism.issueIdentifier10
prism.number103142
prism.publicationDate2021
prism.publicationNameiScience
prism.startingPage103142
prism.volume24
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
pubs.licence-identifierapollo-deposit-licence-2-1
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1016/j.isci.2021.103142

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