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Welz, Patrick-Simon; Zinna, Valentina M.; Symeonidi, Aikaterini; Koronowski, Kevin B.; Kinouchi, Kenichiro; Smith, Jacob G.; Marin Guillen, Ines; Castellanos, Andres; Crainiciuc, Georgiana; Prats, Neus; Martin Caballero, Juan; Hidalgo, Andres; Sassone-Corsi, Paolo and Aznar Benitah, Salvador (2019): BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis. In: Cell, Vol. 177, No. 6

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Abstract

Circadian rhythms control organismal physiology throughout the day. At the cellular level, clock regulation is established by a self-sustained Bmal1 -dependent transcriptional oscillator network. However, it is still unclear how different tissues achieve a synchronized rhythmic physiology. That is, do they respond independently to environmental signals, or require interactions with each other to do so? We show that unexpectedly, light synchronizes the Bmal1-dependent circadian machinery in single tissues in the absence of Bmal1 in all other tissues. Strikingly, light-driven tissue autonomous clocks occur without rhythmic feeding behavior and are lost in constant darkness. Importantly, tissue-autonomous Bmal1 partially sustains homeostasis in otherwise arrhythmic and prematurely aging animals. Our results therefore support a two-branched model for the daily synchronization of tissues: an autonomous response branch, whereby light entrains circadian clocks without any commitment of other Small-dependent clocks, and a memory branch using other Bmal1-dependent clocks to "remember" time in the absence of external cues.

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