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

Author:

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

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.

Funder

Swiss National Science Foundation

European Research Council

State of Geneva

Louis Jeantet Foundation of Medicine

SGED/SSED Young Investigator grant. Work in the laboratory of C.D. was supported by SNSF

SNSF

Vontobel Foundation, the Novartis Consumer Health Foundation

Novartis Consumer Health Foundation, the Swiss Life Foundation

Swiss Life Foundation, the EFSD/Novo

EFSD/Novo Nordisk Program for Diabetes Research in Europe

Olga Mayenfisch Foundation

National Institutes of Health

State of Vaud

Center of Biomedical Research and Education

Publisher

Cold Spring Harbor Laboratory

Subject

Developmental Biology,Genetics

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