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
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