Abstract
BackgroundIn Caenorhabditis elegans early embryo, cell cycles only have two phases: DNA synthesis and mitosis, which are different from the typical 4-phase cell cycle. Modeling this cell-cycle process into network can fill up the gap in C. elegans cell-cycle study and provide a thorough understanding on the cell-cycle regulations and progressions at the network level.MethodsIn this paper, C. elegans early embryonic cell-cycle network has been constructed based on the knowledge of key regulators and their interactions from literature studies. A discrete dynamical Boolean model has been applied in computer simulations to study dynamical properties of this network. The cell-cycle network is compared with random networks and tested under several perturbations to analyze its robustness. To investigate whether our proposed network could explain biological experiment results, we have also compared the network simulation results with gene knock down experiment data.ResultsWith the Boolean model, this study showed that the cell-cycle network was stable with a set of attractors (fixed points). A biological pathway was observed in the simulation, which corresponded to a whole cell-cycle progression. The C. elegans network was significantly robust when compared with random networks of the same size because there were less attractors and larger basins than random networks. Moreover, the network was also robust under perturbations with no significant change of the basin size. In addition, the smaller number of attractors and the shorter biological pathway from gene knock down network simulation interpreted the shorter cell-cycle lengths in mutant from the RNAi gene knock down experiment data. Hence, we demonstrated that the results in network simulation could be verified by the RNAi gene knock down experiment data.ConclusionsA C. elegans early embryonic cell cycles network was constructed and its properties were analyzed and compared with those of random networks. Computer simulation results provided biologically meaningful interpretations of RNAi gene knock down experiment data.
Highlights
In Caenorhabditis elegans early embryo, cell cycles only have two phases: DNA synthesis and mitosis, which are different from the typical 4-phase cell cycle
Simulation of the C. elegans early embryonic cell cycle network To study the dynamical properties of the C. elegans early embryonic cell cycle network, we simulated the changing of each gene or protein’s value in the network by the Booleans functions at different time points
We found that all initial states would converge to five different attractors, which represented the dynamical results of the C. elegans network model
Summary
In Caenorhabditis elegans early embryo, cell cycles only have two phases: DNA synthesis and mitosis, which are different from the typical 4-phase cell cycle. Modeling this cell-cycle process into network can fill up the gap in C. elegans cell-cycle study and provide a thorough understanding on the cell-cycle regulations and progressions at the network level. G1 and G2 phases are “Gap” phases, in which the G1 phase connects the end of the M phase of last cell-cycle to the beginning of the S phase in present cell-cycle, while the G2 phase ensures cell entering into the M phase correctly This mechanism is controlled by several regulators, which are able to interact with each other to achieve complex regulatory functions
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