Tsai2014 - Cell cycle duration control by oscillatory Dynamics in Early Xenopus laevis Embryos

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Short description

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.

Format
SBML (L2V4)
Related Publication
  • Changes in oscillatory dynamics in the cell cycle of early Xenopus laevis embryos.
  • Tsai TY, Theriot JA, Ferrell JE Jr
  • PLoS biology , 2/ 2014 , Volume 12 , Issue 2 , pages: e1001788
  • Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California, United States of America ; Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America ; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, United States of America.
  • 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.
Contributors
Matthieu MAIRE, Ashley Xavier

Metadata information

hasTaxon
Taxonomy Xenopus laevis
hasPart
Gene Ontology regulation of cell cycle
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model
Curation status
Curated
Name Description Size Actions

Model file

Tsai2014.xml SBML L2V4 representation of Tsai2014 - Cell cycle duration control by oscillatory Dynamics in Early Xenopus laevis Embryos 61.74 KB Preview | Download

Additional files

Tsai2014.cps copasi file to generate figure 5F 98.36 KB Preview | Download
tsai2014.sedml SEDML file for reproducing figure 5F(iv) in the reference publication. 8.36 KB Preview | Download

  • Model originally submitted by : Matthieu MAIRE
  • Submitted: 06-Sep-2018 14:33:23
  • Last Modified: 07-Nov-2018 15:23:47
Revisions
  • Version: 5 public model Download this version
    • Submitted on: 07-Nov-2018 15:23:47
    • Submitted by: Ashley Xavier
    • With comment: Automatically added model identifier BIOMD0000000719
  • Version: 2 public model Download this version
    • Submitted on: 06-Sep-2018 14:33:23
    • Submitted by: Matthieu MAIRE
    • With comment: Edited model metadata online.
Curator's comment:
(added: 06 Sep 2018, 14:34:51, updated: 07 Nov 2018, 15:23:16)
Figure 5F of the reference publication has been reproduced using Copasi 4.24 (Build 196). The figures were generated in R 3.5.1.