Development of organisms is a very complex process in that a lot of gene networks of different cell types are to be integrated. Development of cellular automata that model the morphodynamics of different cell types is the first step in understanding and analyzing the regulatory mechanisms that underlie the developmental gene networks. We have developed a model of a cellular automaton that simulates the embryonic development of the shoot meristem in Arabidopsis thaliana. The model adequately describes the basic stages in the development of this organ in wild type and mutants.
相似文献Background
Recent experimental work has uncovered some of the genetic components required to maintain the Arabidopsis thaliana root stem cell niche (SCN) and its structure. Two main pathways are involved. One pathway depends on the genes SHORTROOT and SCARECROW and the other depends on the PLETHORA genes, which have been proposed to constitute the auxin readouts. Recent evidence suggests that a regulatory circuit, composed of WOX5 and CLE40, also contributes to the SCN maintenance. Yet, we still do not understand how the niche is dynamically maintained and patterned or if the uncovered molecular components are sufficient to recover the observed gene expression configurations that characterize the cell types within the root SCN. Mathematical and computational tools have proven useful in understanding the dynamics of cell differentiation. Hence, to further explore root SCN patterning, we integrated available experimental data into dynamic Gene Regulatory Network (GRN) models and addressed if these are sufficient to attain observed gene expression configurations in the root SCN in a robust and autonomous manner.Results
We found that an SCN GRN model based only on experimental data did not reproduce the configurations observed within the root SCN. We developed several alternative GRN models that recover these expected stable gene configurations. Such models incorporate a few additional components and interactions in addition to those that have been uncovered. The recovered configurations are stable to perturbations, and the models are able to recover the observed gene expression profiles of almost all the mutants described so far. However, the robustness of the postulated GRNs is not as high as that of other previously studied networks.Conclusions
These models are the first published approximations for a dynamic mechanism of the A. thaliana root SCN cellular pattering. Our model is useful to formally show that the data now available are not sufficient to fully reproduce root SCN organization and genetic profiles. We then highlight some experimental holes that remain to be studied and postulate some novel gene interactions. Finally, we suggest the existence of a generic dynamical motif that can be involved in both plant and animal SCN maintenance. 相似文献Receptor-mediated endocytosis of low-density lipoproteins, their transport within endosomes, and subsequent degradation in lysosomes are essential components of the molecular system for cholesterol homeostasis in vertebrate cells. The system under study is also an example of clathrin-mediated endocytosis, a possible way of cell communication with the environment. Construction of a detailed mathematical model of this system would allow comprehensive study of mechanisms and kinetics of molecular processes and evaluation of the effect of various mutations, disorders, and environmental changes on the system operation. Receptor-mediated endocytosis of low-density lipoprotein particles and their subsequent degradation in the cell have been modeled. A network of mono-and bimolecular reactions best describing the system has been proposed. The results of calculation of kinetic parameters of the molecular system obtained with the model are in agreement with experimental evidence.
相似文献Nowadays, search for efficient pharmaceuticals against hepatitis C virus (HCV) is an urgent task. In addition to conventional medicines, such as interferon and ribavirin, new specific drugs are being developed. Recently, it has been shown that a peptidomimetic substance, competitive inhibitor of viral NS3 protease, efficiently suppresses replication of the viral RNA replicon in Huh-7 cells. Computer simulation of the operation of the gene network comprising major processes of the viral RNA in the cell provides grounds for analysis of the HCV life cycle and search for key targets for efficient attack with drugs. The gene network of viral RNA replication in Huh-7 cells in the presence of a highly specific and efficient viral NS3 protease inhibitor has been reconstructed by analysis of reported experimental results and application of the GenNet technology. A mathematical model describing the operation of this network has been developed. The kinetics of the decrease in the level of viral RNA in the presence of the inhibitor predicted on the basis of this model is close to experimental results.
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