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Dynamical modeling of syncytial mitotic cycles in Drosophila embryos.

Calzone L, Thieffry D, Tyson JJ, Novak B - Mol. Syst. Biol. (2007)

Bottom Line: During these mitotic cycles, there are barely detectable oscillations in the total level of B-type cyclins.Bifurcation analysis of the differential equations reveals the dependence of mitotic oscillations on cycle number, and how this dependence is altered by mutations.The model can be used to predict the phenotypes of novel mutations and effective ranges of the unmeasured rate constants and transport coefficients in the proposed mechanism.

View Article: PubMed Central - PubMed

Affiliation: Molecular Network Dynamics Research Group of Hungarian Academy of Sciences and Budapest University of Technology and Economics, Budapest, Gellért tér, Hungary.

ABSTRACT
Immediately following fertilization, the fruit fly embryo undergoes 13 rapid, synchronous, syncytial nuclear division cycles driven by maternal genes and proteins. During these mitotic cycles, there are barely detectable oscillations in the total level of B-type cyclins. In this paper, we propose a dynamical model for the molecular events underlying these early nuclear division cycles in Drosophila. The model distinguishes nuclear and cytoplasmic compartments of the embryo and permits exploration of a variety of rules for protein transport between the compartments. Numerical simulations reproduce the main features of wild-type mitotic cycles: patterns of protein accumulation and degradation, lengthening of later cycles, and arrest in interphase 14. The model is consistent with mutations that introduce subtle changes in the number of mitotic cycles before interphase arrest. Bifurcation analysis of the differential equations reveals the dependence of mitotic oscillations on cycle number, and how this dependence is altered by mutations. The model can be used to predict the phenotypes of novel mutations and effective ranges of the unmeasured rate constants and transport coefficients in the proposed mechanism.

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Time-courses of protein concentration, for the case where StringT is not constant. (A) Concentrations of cytoplasmic MPF, Wee1 and String, along with the total amount of CycB. (B) The same proteins acting in the nuclei. (C) Total concentration of String protein in the cell, along with the total concentration of phosphorylated String. (D) Dynamics of maternal string mRNA (Stgm) and the message and protein levels of ‘factor X' (Xm and Xp).
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f3: Time-courses of protein concentration, for the case where StringT is not constant. (A) Concentrations of cytoplasmic MPF, Wee1 and String, along with the total amount of CycB. (B) The same proteins acting in the nuclei. (C) Total concentration of String protein in the cell, along with the total concentration of phosphorylated String. (D) Dynamics of maternal string mRNA (Stgm) and the message and protein levels of ‘factor X' (Xm and Xp).

Mentions: With these amendments to the model, a better description of the early cell cycles in Drosophila is achieved (Figure 3). The levels of String message and protein change as observed in Edgar's experiments (Edgar and Datar, 1996) and the embryo arrests solidly in interphase of cycle 14. In the simulation (Figure 3C), oscillations in String phosphorylation become noticeable around cycle 8, whereas, in experiments, fluctuations in String phosphorylation are already observed in cycle 5 or 6 (Edgar et al, 1994b).


Dynamical modeling of syncytial mitotic cycles in Drosophila embryos.

Calzone L, Thieffry D, Tyson JJ, Novak B - Mol. Syst. Biol. (2007)

Time-courses of protein concentration, for the case where StringT is not constant. (A) Concentrations of cytoplasmic MPF, Wee1 and String, along with the total amount of CycB. (B) The same proteins acting in the nuclei. (C) Total concentration of String protein in the cell, along with the total concentration of phosphorylated String. (D) Dynamics of maternal string mRNA (Stgm) and the message and protein levels of ‘factor X' (Xm and Xp).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1943426&req=5

f3: Time-courses of protein concentration, for the case where StringT is not constant. (A) Concentrations of cytoplasmic MPF, Wee1 and String, along with the total amount of CycB. (B) The same proteins acting in the nuclei. (C) Total concentration of String protein in the cell, along with the total concentration of phosphorylated String. (D) Dynamics of maternal string mRNA (Stgm) and the message and protein levels of ‘factor X' (Xm and Xp).
Mentions: With these amendments to the model, a better description of the early cell cycles in Drosophila is achieved (Figure 3). The levels of String message and protein change as observed in Edgar's experiments (Edgar and Datar, 1996) and the embryo arrests solidly in interphase of cycle 14. In the simulation (Figure 3C), oscillations in String phosphorylation become noticeable around cycle 8, whereas, in experiments, fluctuations in String phosphorylation are already observed in cycle 5 or 6 (Edgar et al, 1994b).

Bottom Line: During these mitotic cycles, there are barely detectable oscillations in the total level of B-type cyclins.Bifurcation analysis of the differential equations reveals the dependence of mitotic oscillations on cycle number, and how this dependence is altered by mutations.The model can be used to predict the phenotypes of novel mutations and effective ranges of the unmeasured rate constants and transport coefficients in the proposed mechanism.

View Article: PubMed Central - PubMed

Affiliation: Molecular Network Dynamics Research Group of Hungarian Academy of Sciences and Budapest University of Technology and Economics, Budapest, Gellért tér, Hungary.

ABSTRACT
Immediately following fertilization, the fruit fly embryo undergoes 13 rapid, synchronous, syncytial nuclear division cycles driven by maternal genes and proteins. During these mitotic cycles, there are barely detectable oscillations in the total level of B-type cyclins. In this paper, we propose a dynamical model for the molecular events underlying these early nuclear division cycles in Drosophila. The model distinguishes nuclear and cytoplasmic compartments of the embryo and permits exploration of a variety of rules for protein transport between the compartments. Numerical simulations reproduce the main features of wild-type mitotic cycles: patterns of protein accumulation and degradation, lengthening of later cycles, and arrest in interphase 14. The model is consistent with mutations that introduce subtle changes in the number of mitotic cycles before interphase arrest. Bifurcation analysis of the differential equations reveals the dependence of mitotic oscillations on cycle number, and how this dependence is altered by mutations. The model can be used to predict the phenotypes of novel mutations and effective ranges of the unmeasured rate constants and transport coefficients in the proposed mechanism.

Show MeSH
Related in: MedlinePlus