Circadian hepatocyte clocks keep synchrony in the absence of a master pacemaker in the suprachiasmatic nucleus or other extrahepatic clocks

Flore Sinturel; Pascal Gos; Volodymyr Petrenko; Claudia Hagedorn; Florian Kreppel; Kai-Florian Storch; Darko Knutti; Andre Liani; Charles Weitz; Yann Emmenegger; Paul Franken; Luigi Bonacina; Charna Dibner; Ueli Schibler

doi:10.1101/gad.346460.120

Circadian hepatocyte clocks keep synchrony in the absence of a master pacemaker in the suprachiasmatic nucleus or other extrahepatic clocks

Genes Dev. 2021 Mar 1;35(5-6):329-334. doi: 10.1101/gad.346460.120. Epub 2021 Feb 18.

Authors

Flore Sinturel^#^{1

2

3

4}, Pascal Gos^#⁵, Volodymyr Petrenko^{1

2

3

4}, Claudia Hagedorn⁶, Florian Kreppel⁶, Kai-Florian Storch⁷, Darko Knutti⁷, Andre Liani⁵, Charles Weitz⁷, Yann Emmenegger⁸, Paul Franken⁸, Luigi Bonacina⁹, Charna Dibner^{1

2

3

4}, Ueli Schibler⁵

Affiliations

¹ Department of Medicine, Division of Endocrinology, Diabetes, Nutrition, and Patient Education, University Hospital of Geneva, 1211 Geneva, Switzerland.
² Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
³ Institute of Genetics and Genomics of Geneva (iGE3), 1211 Geneva, Switzerland.
⁴ Diabetes Center, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
⁵ Department of Molecular Biology, Sciences III, University of Geneva, 1211 Geneva, Switzerland.
⁶ Center of Biomedical Education and Research, University Witten/Herdecke, 58448 Witten, Germany.
⁷ Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
⁸ Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.
⁹ Department of Applied Physics, University of Geneva, 1211 Geneva, Switzerland.

^# Contributed equally.

Abstract

It has been assumed that the suprachiasmatic nucleus (SCN) synchronizes peripheral circadian oscillators. However, this has never been convincingly shown, since biochemical time series experiments are not feasible in behaviorally arrhythmic animals. By using long-term bioluminescence recording in freely moving mice, we show that the SCN is indeed required for maintaining synchrony between organs. Surprisingly, however, circadian oscillations persist in the livers of mice devoid of an SCN or oscillators in cells other than hepatocytes. Hence, similar to SCN neurons, hepatocytes can maintain phase coherence in the absence of Zeitgeber signals produced by other organs or environmental cycles.

Keywords: circadian gene expression; in vivo bioluminescence recording; liver; suprachiasmatic nucleus.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Circadian Clocks / genetics
Circadian Clocks / physiology*
Gene Expression Regulation
Hepatocytes / physiology*
Male
Mice
Mice, Inbred C57BL
Suprachiasmatic Nucleus / physiology*
Suprachiasmatic Nucleus / surgery

Grants and funding

R01 NS055831/NS/NINDS NIH HHS/United States