ZFIN ID: ZDB-PUB-180626-8
Interactions between the circadian clock and TGF-β signaling pathway in zebrafish
Sloin, H.E., Ruggiero, G., Rubinstein, A., Smadja Storz, S., Foulkes, N.S., Gothilf, Y.
Date: 2018
Source: PLoS One   13: e0199777 (Journal)
Registered Authors: Foulkes, Nicholas-Simon, Gothilf, Yoav
Keywords: none
MeSH Terms:
  • Animals
  • Cell Line
  • Circadian Clocks/physiology*
  • Female
  • Gene Expression Regulation/physiology*
  • Male
  • Period Circadian Proteins/biosynthesis*
  • Period Circadian Proteins/genetics
  • Signal Transduction/physiology*
  • Smad3 Protein/genetics
  • Smad3 Protein/metabolism*
  • Transforming Growth Factor beta/genetics
  • Transforming Growth Factor beta/metabolism*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/biosynthesis*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 29940038 Full text @ PLoS One
TGF-β signaling is a cellular pathway that functions in most cells and has been shown to play a role in multiple processes, such as the immune response, cell differentiation and proliferation. Recent evidence suggests a possible interaction between TGF-β signaling and the molecular circadian oscillator. The current study aims to characterize this interaction in the zebrafish at the molecular and behavioral levels, taking advantage of the early development of a functional circadian clock and the availability of light-entrainable clock-containing cell lines.
Smad3a, a TGF-β signaling-related gene, exhibited a circadian expression pattern throughout the brain of zebrafish larvae. Both pharmacological inhibition and indirect activation of TGF-β signaling in zebrafish Pac-2 cells caused a concentration dependent disruption of rhythmic promoter activity of the core clock gene Per1b. Inhibition of TGF-β signaling in intact zebrafish larvae caused a phase delay in the rhythmic expression of Per1b mRNA. TGF-β inhibition also reversibly disrupted, phase delayed and increased the period of circadian rhythms of locomotor activity in zebrafish larvae.
The current research provides evidence for an interaction between the TGF-β signaling pathway and the circadian clock system at the molecular and behavioral levels, and points to the importance of TGF-β signaling for normal circadian clock function. Future examination of this interaction should contribute to a better understanding of its underlying mechanisms and its influence on a variety of cellular processes including the cell cycle, with possible implications for cancer development and progression.