Tsai2014 - Cell cycle duration control by oscillatory Dynamics in Early Xenopus laevis Embryos
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.
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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 , PubMed ID: 24523664
- 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.
Submitter of this revision: Ashley Xavier
Modellers: Matthieu MAIRE, Ashley Xavier
Metadata information
hasTaxon (1 statement)
hasPart (1 statement)
hasProperty (1 statement)
isDescribedBy (2 statements)
Connected external resources
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| Name | Description | Size | Actions |
|---|---|---|---|
Model files |
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| 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 |
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| 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: Sep 6, 2018 2:33:23 PM
- Last Modified: Nov 7, 2018 3:23:47 PM
Revisions
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Version: 5
- Submitted on: Nov 7, 2018 3:23:47 PM
- Submitted by: Ashley Xavier
- With comment: Automatically added model identifier BIOMD0000000719
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Version: 2
- Submitted on: Sep 6, 2018 2:33:23 PM
- Submitted by: Matthieu MAIRE
- With comment: Edited model metadata online.
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: Variable used inside SBML models
| Species | Initial Concentration/Amount |
|---|---|
| Cyclin B1 Cdk1 complex phosphorylated G2/mitotic-specific cyclin-B1 ; Cyclin-dependent kinase 1-A ; protein-containing complex |
60.0 mmol |
| Cyclin B1 Cdk1 complex unphosphorylated G2/mitotic-specific cyclin-B1 ; Cyclin-dependent kinase 1-A ; protein-containing complex |
0.0 mmol |
| Plx1 active Serine/threonine-protein kinase PLK1 ; active |
0.0 mmol |
| APC C active Anaphase-promoting complex subunit 16 ; active |
1.0 mmol |
| Cyclin B1 Cdk1 complex total Cyclin-dependent kinase 1-A ; G2/mitotic-specific cyclin-B1 ; protein-containing complex |
60.0 mmol |
| Reactions | Rate | Parameters |
|---|---|---|
| Cyclin_B1_Cdk1_complex_phosphorylated => ; APC_C_active | nuclear*k_dest*APC_C_active*Cyclin_B1_Cdk1_complex_phosphorylated | k_dest = 0.4 |
| Cyclin_B1_Cdk1_complex_unphosphorylated => Cyclin_B1_Cdk1_complex_phosphorylated | nuclear*1/r^(1/2)*k_cdk1_on*(1+p/(1+(ec50_cdc25/Cyclin_B1_Cdk1_complex_phosphorylated)^n_cdc25))*Cyclin_B1_Cdk1_complex_unphosphorylated | k_cdk1_on = 0.0354; n_cdc25 = 11.0; r = 0.499999924670036; ec50_cdc25 = 30.0; p = 5.0 |
| => Plx1_active; Cyclin_B1_Cdk1_complex_phosphorylated, Plx1_total | nuclear*k_plxon/(1+(ec50_plx/Cyclin_B1_Cdk1_complex_phosphorylated)^n_plx)*(Plx1_total-Plx1_active) | ec50_plx = 60.0; n_plx = 5.0; k_plxon = 1.5 |
| APC_C_active => | nuclear*k_apc_off*APC_C_active | k_apc_off = 0.15 |
| Cyclin_B1_Cdk1_complex_phosphorylated => Cyclin_B1_Cdk1_complex_unphosphorylated | nuclear*r^(1/2)*k_cdk1_off*(1+p/((Cyclin_B1_Cdk1_complex_phosphorylated/ec50_wee1)^n_wee1+1))*Cyclin_B1_Cdk1_complex_phosphorylated | k_cdk1_off = 0.0354; r = 0.499999924670036; n_wee1 = 3.5; p = 5.0; ec50_wee1 = 35.0 |
| => APC_C_active; Plx1_active, APC_C_total | nuclear*k_apc_on/(1+(ec50_apc/Plx1_active)^n_apc)*(APC_C_total-APC_C_active) | n_apc = 4.0; k_apc_on = 1.5; ec50_apc = 0.5 |
| Plx1_active => | nuclear*k_plx_off*Plx1_active | k_plx_off = 0.125 |
| Cyclin_B1_Cdk1_complex_total = Cyclin_B1_Cdk1_complex_unphosphorylated+Cyclin_B1_Cdk1_complex_phosphorylated | [] | [] |
| => Cyclin_B1_Cdk1_complex_phosphorylated | nuclear*k_synth | k_synth = 1.5 |
(added: 06 Sep 2018, 14:34:51, updated: 07 Nov 2018, 15:23:16)