Identification of pathways that regulate circadian rhythms using a larval zebrafish small molecule screen

Eric Ardon Mosser, Cindy N. Chiu, T. Katherine Tamai, Tsuyoshi Hirota, Suna Li, May Hui, Amy Wang, Chanpreet Singh, Andrew Giovanni, Steve A. Kay, David A. Prober*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


The circadian clock ensures that behavioral and physiological processes occur at appropriate times during the 24-hour day/night cycle, and is regulated at both the cellular and organismal levels. To identify pathways acting on intact animals, we performed a small molecule screen using a luminescent reporter of molecular circadian rhythms in zebrafish larvae. We identified both known and novel pathways that affect circadian period, amplitude and phase. Several drugs identified in the screen did not affect circadian rhythms in cultured cells derived from luminescent reporter embryos or in established zebrafish and mammalian cell lines, suggesting they act via mechanisms absent in cell culture. Strikingly, using drugs that promote or inhibit inflammation, as well as a mutant that lacks microglia, we found that inflammatory state affects circadian amplitude. These results demonstrate a benefit of performing drug screens using intact animals and provide novel targets for treating circadian rhythm disorders.

Original languageEnglish (US)
Article number12405
JournalScientific reports
Issue number1
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • General


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