The systemic control of circadian gene expression.
The mammalian circadian timing system consists of a central pacemaker in the brain's suprachiasmatic nucleus (SCN) and subsidiary oscillators in nearly all body cells. The SCN clock, which is adjusted to geophysical time by the photoperiod, synchronizes peripheral clocks through a wide variety of systemic cues. The latter include signals depending on feeding cycles, glucocorticoid hormones, rhythmic blood-borne signals eliciting daily changes in actin dynamics and serum response factor (SRF) activity, and sensors of body temperature rhythms, such as heat shock transcription factors and the cold-inducible RNA-binding protein CIRP. To study these systemic signalling pathways, we designed and engineered a novel, highly photosensitive apparatus, dubbed RT-Biolumicorder. This device enables us to record circadian luciferase reporter gene expression in the liver and other organs of freely moving mice over months in real time. Owing to the multitude of systemic signalling pathway involved in the phase resetting of peripheral clocks the disruption of any particular one has only minor effects on the steady state phase of circadian gene expression in organs such as the liver. Nonetheless, the implication of specific pathways in the synchronization of clock gene expression can readily be assessed by monitoring the phase-shifting kinetics using the RT-Biolumicorder.
Department of Molecular Biology, University of Geneva, Geneva, Switzerland.|Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, NY, USA.
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Gerber
Department of Molecular Biology, University of Geneva, Geneva, Switzerland.|Laboratory of Circadian Endocrinology, Geneva University Hospitals, Geneva, Switzerland.
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C
Saini
Center of Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
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Curie
Center of Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
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Emmenegger
Department of Molecular Biology, University of Geneva, Geneva, Switzerland.
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Rando
Department of Molecular Biology, University of Geneva, Geneva, Switzerland.
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Gosselin
Department of Molecular Biology, University of Geneva, Geneva, Switzerland.
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Gotic
Department of Molecular Biology, University of Geneva, Geneva, Switzerland.
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Gos
Center of Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
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Franken
Department of Molecular Biology, University of Geneva, Geneva, Switzerland.
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Schibler
D000818:Animals; D056926:CLOCK Proteins / Q000378:metabolism*; D057906:Circadian Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D004867:Equipment Design; D015870:Gene Expression; D017930:Genes, Reporter / Q000502:physiology; D005938:Glucocorticoids / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction / Q000235:genetics*; D013493:Suprachiasmatic Nucleus / Q000502:physiology*
D005938:Glucocorticoids; D008156:Luciferases; D056926:CLOCK Proteins
actin dynamics; body temperature rhythms; circadian clock; feeding rhythms; glucocorticoid hormones; peripheral oscillators; serum response factor (SRF); synchronization