PUBLICATION

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

Authors
Mosser, E.A., Chiu, C.N., Tamai, T.K., Hirota, T., Li, S., Hui, M., Wang, A., Singh, C., Giovanni, A., Kay, S.A., Prober, D.A.
ID
ZDB-PUB-190830-4
Date
2019
Source
Scientific Reports   9: 12405 (Journal)
Registered Authors
Li, Suna, Prober, David, Tamai, Takako Katherine
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified/physiology
  • Anti-Inflammatory Agents, Non-Steroidal/pharmacology
  • Casein Kinase I/antagonists & inhibitors
  • Casein Kinase I/metabolism
  • Circadian Rhythm/drug effects*
  • Larva/drug effects
  • Larva/physiology
  • Protein Kinase Inhibitors/pharmacology
  • Receptors, Glycine/agonists
  • Receptors, Glycine/metabolism
  • Small Molecule Libraries/pharmacology*
  • Taurine/pharmacology
  • Zebrafish/growth & development
  • Zebrafish/physiology*
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/metabolism
PubMed
31455847 Full text @ Sci. Rep.
Abstract
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes