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

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

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19 Citations (Scopus)

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. Light can synchronize circadian clocks within the epidermis in the absence of BMAL1-driven clocks in all other tissues.

Original languageEnglish
Pages (from-to)1436-1447.e12
JournalCell
Volume177
Issue number6
DOIs
Publication statusPublished - 2019 May 30

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Welz, P. S., Zinna, V. M., Symeonidi, A., Koronowski, K. B., Kinouchi, K., Smith, J. G., Guillén, I. M., Castellanos, A., Crainiciuc, G., Prats, N., Caballero, J. M., Hidalgo, A., Sassone-Corsi, P., & Benitah, S. A. (2019). BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis. Cell, 177(6), 1436-1447.e12. https://doi.org/10.1016/j.cell.2019.05.009