BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis

BMAL1驱动的组织时钟独立于光照做出反应以维持体内平衡

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作者:Patrick-Simon Welz ,Valentina M Zinna ,Aikaterini Symeonidi ,Kevin B Koronowski ,Kenichiro Kinouchi ,Jacob G Smith ,Inés Marín Guillén ,Andrés Castellanos ,Stephen Furrow ,Ferrán Aragón ,Georgiana Crainiciuc ,Neus Prats ,Juan Martín Caballero ,Andrés Hidalgo ,Paolo Sassone-Corsi ,Salvador Aznar Benitah

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 Bmal1-dependent clocks, and a memory branch using other Bmal1-dependent clocks to "remember" time in the absence of external cues.

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