Glucocorticoids Play a Key Role in Circadian Cell Cycle Rhythms
- Dickmeis, T., Lahiri, K., Nica, G., Vallone, D., Santoriello, C., Neumann, C.J., Hammerschmidt, M., and Foulkes, N.S.
- 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
- Cell cycle and cell division, Circadian rhythms, Larvae, Pituitary gland, Zebrafish, Hydrocortisone, Circadian oscillators, Gene expression
- MeSH Terms
- Cell Cycle/physiology*
- Cell Proliferation
- Circadian Rhythm*
- Molecular Sequence Data
- 17373855 Full text @ PLoS Biol.
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.
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
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes