PUBLICATION

Glucocorticoids Play a Key Role in Circadian Cell Cycle Rhythms

Authors
Dickmeis, T., Lahiri, K., Nica, G., Vallone, D., Santoriello, C., Neumann, C.J., Hammerschmidt, M., and Foulkes, N.S.
ID
ZDB-PUB-070330-27
Date
2007
Source
PLoS Biology   5(4): e78 (Journal)
Registered Authors
Dickmeis, Thomas, Foulkes, Nicholas-Simon, Hammerschmidt, Matthias, Lahiri, Kajori, Neumann, Carl J., Nica, Gabriela, Santoriello, Cristina, Vallone, Daniela
Keywords
Cell cycle and cell division, Circadian rhythms, Larvae, Pituitary gland, Zebrafish, Hydrocortisone, Circadian oscillators, Gene expression
MeSH Terms
  • Circadian Rhythm*
  • Animals
  • Cell Proliferation
  • Hydrocortisone/physiology*
  • Molecular Sequence Data
  • Mutation
  • Zebrafish
  • Cell Cycle/physiology*
(all 8)
PubMed
17373855 Full text @ PLoS Biol.
Abstract
Clock output pathways play a pivotal role by relaying timing information from the circadian clock to a diversity of physiological systems. Both cell-autonomous and systemic mechanisms have been implicated as clock outputs; however, the relative importance and interplay between these mechanisms are poorly understood. The cell cycle represents a highly conserved regulatory target of the circadian timing system. Previously, we have demonstrated that in zebrafish, the circadian clock has the capacity to generate daily rhythms of S phase by a cell-autonomous mechanism in vitro. Here, by studying a panel of zebrafish mutants, we reveal that the pituitary-adrenal axis also plays an essential role in establishing these rhythms in the whole animal. Mutants with a reduction or a complete absence of corticotrope pituitary cells show attenuated cell-proliferation rhythms, whereas expression of circadian clock genes is not affected. We show that the corticotrope deficiency is associated with reduced cortisol levels, implicating glucocorticoids as a component of a systemic signaling pathway required for circadian cell cycle rhythmicity. Strikingly, high-amplitude rhythms can be rescued by exposing mutant larvae to a tonic concentration of a glucocorticoid agonist. Our work suggests that cell-autonomous clock mechanisms are not sufficient to establish circadian cell cycle rhythms at the whole-animal level. Instead, they act in concert with a systemic signaling environment of which glucocorticoids are an essential part.
Genes / Markers
Figures
Figure Gallery (7 images)
Show all Figures
Expression
Phenotype
Fish Conditions Stage Phenotype Figure
rx3t25327/t25327standard conditionsDay 6
rx3t25327/t25327standard conditionsDay 6
1 - 2 of 2
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
t21379
    		Point Mutation
    t22072
      		Point Mutation
      t22744
        		Point Mutation
        t24149
          		Point Mutation
          t25181
            		Point Mutation
            t25327
              		Point Mutation
              t26212
                		Point Mutation
                1 - 7 of 7
                Show
                Human Disease / Model
                No data available
                Sequence Targeting Reagents
                No data available
                Fish
                Fish
                eya1t22744/t22744
                fgf3t24149/t24149
                fgf3t26212/t26212
                pou1f1t21379/t21379
                pou1f1t22072/t22072
                rx3t25181/t25181
                rx3t25327/t25327
                WT
                1 - 8 of 8
                Show
                Antibodies
                Name Type Antigen Genes Isotypes Host Organism
                Ab1-nr3c1polyclonal
                  		IgGRabbit
                  1 - 1 of 1
                  Show
                  Orthology
                  No data available
                  Engineered Foreign Genes
                  No data available
                  Mapping
                  No data available
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                  Citation
                  Dickmeis, T., Lahiri, K., Nica, G., Vallone, D., Santoriello, C., Neumann, C.J., Hammerschmidt, M., and Foulkes, N.S. (2007) Glucocorticoids Play a Key Role in Circadian Cell Cycle Rhythms. PLoS Biology. 5(4):e78.