Interactions between the circadian clock and TGF-β signaling pathway in zebrafish
Autor: | Yoav Gothilf, Amir Rubinstein, Hadas E. Sloin, Nicholas S. Foulkes, Sima Smadja Storz, Gennaro Ruggiero |
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Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Life Cycles Cell signaling Cellular differentiation Circadian clock lcsh:Medicine Gene Expression Signal transduction Biochemistry Larvae Transforming Growth Factor beta lcsh:Science Zebrafish Multidisciplinary Signaling cascades Eukaryota Animal Models Period Circadian Proteins Cell cycle Cell biology CLOCK Circadian Rhythms Circadian Oscillators Experimental Organism Systems Osteichthyes Vertebrates Female Research Article Life sciences biology SMAD signaling Period (gene) Biology Research and Analysis Methods Cell Line 03 medical and health sciences Model Organisms Circadian Clocks ddc:570 Genetics Animals Smad3 Protein Circadian rhythm lcsh:R Organisms Biology and Life Sciences Zebrafish Proteins biology.organism_classification Fish 030104 developmental biology TGF-beta signaling cascade Gene Expression Regulation lcsh:Q Chronobiology Developmental Biology |
Zdroj: | PLoS one, 13 (6), e0199777 PLoS ONE PLoS ONE, Vol 13, Iss 6, p e0199777 (2018) |
ISSN: | 1932-6203 |
DOI: | 10.1371/journal.pone.0199777 |
Popis: | 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. |
Databáze: | OpenAIRE |
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