Dynamical modeling of syncytial mitotic cycles in Drosophila embryos.
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.
Calzone
Laurence
L
Molecular Network Dynamics Research Group of Hungarian Academy of Sciences and Budapest University of Technology and Economics, Budapest, Gellért tér, Hungary.
Thieffry
Denis
D
Tyson
John J
JJ
Novak
Bela
B
D000546:Amanitins / Q000494:pharmacology; D000818:Animals; D003198:Computer Simulation; D016213:Cyclins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000187:drug effects / Q000196:embryology*; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000187:drug effects; D018628:Gene Dosage / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D013997:Time Factors
D000546:Amanitins; D016213:Cyclins