Real-time recording of circadian liver gene expression in freely moving mice reveals the phase-setting behavior of hepatocyte clocks
- Camille Saini1,2,6,
- André Liani1,2,6,
- Thomas Curie3,
- Pascal Gos1,2,
- Florian Kreppel4,
- Yann Emmenegger3,
- Luigi Bonacina5,
- Jean-Pierre Wolf5,
- Yves-Alain Poget1,2,
- Paul Franken3 and
- Ueli Schibler1,2,7
- 1Department of Molecular Biology, Sciences III, University of Geneva, 1211 Geneva, Switzerland;
- 2National Centre of Competence in Research Frontiers in Genetics, 1211 Geneva, Switzerland;
- 3Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland;
- 4Department of Gene Therapy, University of Ulm, D-89081 Ulm, Germany;
- 5GAP-Biophotonics, University of Geneva, 1211 Geneva, Switzerland
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↵6 These authors contributed equally to this work.
Abstract
The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) in the hypothalamus, which is thought to set the phase of slave oscillators in virtually all body cells. However, due to the lack of appropriate in vivo recording technologies, it has been difficult to study how the SCN synchronizes oscillators in peripheral tissues. Here we describe the real-time recording of bioluminescence emitted by hepatocytes expressing circadian luciferase reporter genes in freely moving mice. The technology employs a device dubbed RT-Biolumicorder, which consists of a cylindrical cage with reflecting conical walls that channel photons toward a photomultiplier tube. The monitoring of circadian liver gene expression revealed that hepatocyte oscillators of SCN-lesioned mice synchronized more rapidly to feeding cycles than hepatocyte clocks of intact mice. Hence, the SCN uses signaling pathways that counteract those of feeding rhythms when their phase is in conflict with its own phase.
Keywords
- circadian gene expression
- real-time bioluminescence monitoring
- liver oscillators
- resetting cues
- SCN lesion
Footnotes
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↵7 Corresponding author
E-mail ueli.schibler{at}unige.ch
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.221374.113.
- Received May 6, 2013.
- Accepted June 5, 2013.
- Copyright © 2013 by Cold Spring Harbor Laboratory Press
Freely available online through the Genes & Development Open Access option.