Zfhx3-mediated genetic ablation of the SCN abolishes light entrainable circadian activity while sparing food anticipatory activity.
Wilcox, Ashleigh G
Bains, R Sonia
Oliver, Peter L
Maywood, Elizabeth S
Nolan, Patrick M
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Wilcox, A. G., Bains, R. S., Williams, D., Joynson, E., Vizor, L., Oliver, P. L., Maywood, E. S., et al. (2021). Zfhx3-mediated genetic ablation of the SCN abolishes light entrainable circadian activity while sparing food anticipatory activity.. iScience, 24 (10. 103142), 103142. https://doi.org/10.1016/j.isci.2021.103142
Circadian 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.
Biological sciences, Molecular biology, Neuroscience, Physiology
External DOI: https://doi.org/10.1016/j.isci.2021.103142
This record's URL: https://www.repository.cam.ac.uk/handle/1810/331222
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/