PUBLICATION
Interactions between the circadian clock and TGF-β signaling pathway in zebrafish
- Authors
- Sloin, H.E., Ruggiero, G., Rubinstein, A., Smadja Storz, S., Foulkes, N.S., Gothilf, Y.
- ID
- ZDB-PUB-180626-8
- 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
- CTD
- 29940038
Citation
Sloin, H.E., Ruggiero, G., Rubinstein, A., Smadja Storz, S., Foulkes, N.S., Gothilf, Y. (2018) Interactions between the circadian clock and TGF-β signaling pathway in zebrafish. PLoS One. 13:e0199777.
Abstract
Background 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.
Results 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.
Conclusions 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping