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PLoS Biol 2014 Feb 11;122:e1001788. doi: 10.1371/journal.pbio.1001788.
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Changes in oscillatory dynamics in the cell cycle of early Xenopus laevis embryos.

Tsai TY , Theriot JA , Ferrell JE .

During the early development of Xenopus laevis embryos, the first mitotic cell cycle is long (∼85 min) and the subsequent 11 cycles are short (∼30 min) and clock-like. Here we address the question of how the Cdk1 cell cycle oscillator changes between these two modes of operation. We found that the change can be attributed to an alteration in the balance between Wee1/Myt1 and Cdc25. The change in balance converts a circuit that acts like a positive-plus-negative feedback oscillator, with spikes of Cdk1 activation, to one that acts like a negative-feedback-only oscillator, with a shorter period and smoothly varying Cdk1 activity. Shortening the first cycle, by treating embryos with the Wee1A/Myt1 inhibitor PD0166285, resulted in a dramatic reduction in embryo viability, and restoring the length of the first cycle in inhibitor-treated embryos with low doses of cycloheximide partially rescued viability. Computations with an experimentally parameterized mathematical model show that modest changes in the Wee1/Cdc25 ratio can account for the observed qualitative changes in the cell cycle. The high ratio in the first cycle allows the period to be long and tunable, and decreasing the ratio in the subsequent cycles allows the oscillator to run at a maximal speed. Thus, the embryo rewires its feedback regulation to meet two different developmental requirements during early development.

PubMed ID: 24523664
PMC ID: PMC3921120
Article link: PLoS Biol
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: cdc25a cdc25c cdk1 cdk20 cfp clock mapk1 myt1 rasgrf1 wee1
Antibodies: Cdk1 Ab2
Morpholinos: ccnb1 MO1 ccnb1.2 MO1 cdc25a MO1 cdc25a MO2

Article Images: [+] show captions
References [+] :
Bitangcol, Activation of the p42 mitogen-activated protein kinase pathway inhibits Cdc2 activation and entry into M-phase in cycling Xenopus egg extracts. 1998, Pubmed, Xenbase