Limits...
Dynamical modeling of the cell cycle and cell fate emergence in Caulobacter crescentus.

Quiñones-Valles C, Sánchez-Osorio I, Martínez-Antonio A - PLoS ONE (2014)

Bottom Line: The results of the simulations based on our model show a cyclic attractor whose configurations can be made to correspond with the current knowledge of the activity of the regulators participating in the gene network during the cell cycle.Additionally, we found two point attractors that can be interpreted in terms of the network configurations directing the two cell types.The entire network is shown to be operating close to the critical regime, which means that it is robust enough to perturbations on dynamics of the network, but adaptable to environmental changes.

View Article: PubMed Central - PubMed

Affiliation: Engineering and Biomedical Physics Department, Center for Research and Advanced Studies of the National Polytechnic Institute at Monterrey, Apodaca, Nuevo León, México; Genetic Engineering Department, Center for Research and Advanced Studies of the National Polytechnic Institute at Irapuato, Irapuato, Guanajuato, México.

ABSTRACT
The division of Caulobacter crescentus, a model organism for studying cell cycle and differentiation in bacteria, generates two cell types: swarmer and stalked. To complete its cycle, C. crescentus must first differentiate from the swarmer to the stalked phenotype. An important regulator involved in this process is CtrA, which operates in a gene regulatory network and coordinates many of the interactions associated to the generation of cellular asymmetry. Gaining insight into how such a differentiation phenomenon arises and how network components interact to bring about cellular behavior and function demands mathematical models and simulations. In this work, we present a dynamical model based on a generalization of the Boolean abstraction of gene expression for a minimal network controlling the cell cycle and asymmetric cell division in C. crescentus. This network was constructed from data obtained from an exhaustive search in the literature. The results of the simulations based on our model show a cyclic attractor whose configurations can be made to correspond with the current knowledge of the activity of the regulators participating in the gene network during the cell cycle. Additionally, we found two point attractors that can be interpreted in terms of the network configurations directing the two cell types. The entire network is shown to be operating close to the critical regime, which means that it is robust enough to perturbations on dynamics of the network, but adaptable to environmental changes.

Show MeSH

Related in: MedlinePlus

Regulatory network for the control of the cell cycle in C. crescentus (graph G1).Nodes represent genes/proteins and edges their regulatory interactions. These may be positives (green edges), negatives (red edges) or dual (blue edges). Purple nodes represent transcription factors; the blue node represents the methyl-transferase; the orange nodes correspond to kinases or phosphatases; and the gray node to the CtrA proteolytic complex. Larger nodes and thicker edges represent the core network that is modeled in this work (graphic G2).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4219702&req=5

pone-0111116-g002: Regulatory network for the control of the cell cycle in C. crescentus (graph G1).Nodes represent genes/proteins and edges their regulatory interactions. These may be positives (green edges), negatives (red edges) or dual (blue edges). Purple nodes represent transcription factors; the blue node represents the methyl-transferase; the orange nodes correspond to kinases or phosphatases; and the gray node to the CtrA proteolytic complex. Larger nodes and thicker edges represent the core network that is modeled in this work (graphic G2).

Mentions: A directed graph G1 was drawn from the pairwise regulatory interactions obtained from the literature (see Figure 2). All the biological processes and proteins involved were included. The graph was drawn using Cytoscape [25]. In this abstract structure, the vertices or nodes represent genes or proteins and edges their regulatory interactions. Green edges indicate positive interactions, red edges stand for negative ones, and blue edges represent dual regulatory interactions. The graph contains all the proteins associated to the main transcription factors controlling the processes of DNA-replication and cell division, as well as additional cellular processes linked to the cell cycle, such as polar morphogenesis. Many of these proteins are involved in the development of the stalk or flagellum. The whole network G1 is composed of 153 vertices (V1 = 153) and 212 edges (E1 = 212), supporting information (Table S1, sheet 1 in File S1).


Dynamical modeling of the cell cycle and cell fate emergence in Caulobacter crescentus.

Quiñones-Valles C, Sánchez-Osorio I, Martínez-Antonio A - PLoS ONE (2014)

Regulatory network for the control of the cell cycle in C. crescentus (graph G1).Nodes represent genes/proteins and edges their regulatory interactions. These may be positives (green edges), negatives (red edges) or dual (blue edges). Purple nodes represent transcription factors; the blue node represents the methyl-transferase; the orange nodes correspond to kinases or phosphatases; and the gray node to the CtrA proteolytic complex. Larger nodes and thicker edges represent the core network that is modeled in this work (graphic G2).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4219702&req=5

pone-0111116-g002: Regulatory network for the control of the cell cycle in C. crescentus (graph G1).Nodes represent genes/proteins and edges their regulatory interactions. These may be positives (green edges), negatives (red edges) or dual (blue edges). Purple nodes represent transcription factors; the blue node represents the methyl-transferase; the orange nodes correspond to kinases or phosphatases; and the gray node to the CtrA proteolytic complex. Larger nodes and thicker edges represent the core network that is modeled in this work (graphic G2).
Mentions: A directed graph G1 was drawn from the pairwise regulatory interactions obtained from the literature (see Figure 2). All the biological processes and proteins involved were included. The graph was drawn using Cytoscape [25]. In this abstract structure, the vertices or nodes represent genes or proteins and edges their regulatory interactions. Green edges indicate positive interactions, red edges stand for negative ones, and blue edges represent dual regulatory interactions. The graph contains all the proteins associated to the main transcription factors controlling the processes of DNA-replication and cell division, as well as additional cellular processes linked to the cell cycle, such as polar morphogenesis. Many of these proteins are involved in the development of the stalk or flagellum. The whole network G1 is composed of 153 vertices (V1 = 153) and 212 edges (E1 = 212), supporting information (Table S1, sheet 1 in File S1).

Bottom Line: The results of the simulations based on our model show a cyclic attractor whose configurations can be made to correspond with the current knowledge of the activity of the regulators participating in the gene network during the cell cycle.Additionally, we found two point attractors that can be interpreted in terms of the network configurations directing the two cell types.The entire network is shown to be operating close to the critical regime, which means that it is robust enough to perturbations on dynamics of the network, but adaptable to environmental changes.

View Article: PubMed Central - PubMed

Affiliation: Engineering and Biomedical Physics Department, Center for Research and Advanced Studies of the National Polytechnic Institute at Monterrey, Apodaca, Nuevo León, México; Genetic Engineering Department, Center for Research and Advanced Studies of the National Polytechnic Institute at Irapuato, Irapuato, Guanajuato, México.

ABSTRACT
The division of Caulobacter crescentus, a model organism for studying cell cycle and differentiation in bacteria, generates two cell types: swarmer and stalked. To complete its cycle, C. crescentus must first differentiate from the swarmer to the stalked phenotype. An important regulator involved in this process is CtrA, which operates in a gene regulatory network and coordinates many of the interactions associated to the generation of cellular asymmetry. Gaining insight into how such a differentiation phenomenon arises and how network components interact to bring about cellular behavior and function demands mathematical models and simulations. In this work, we present a dynamical model based on a generalization of the Boolean abstraction of gene expression for a minimal network controlling the cell cycle and asymmetric cell division in C. crescentus. This network was constructed from data obtained from an exhaustive search in the literature. The results of the simulations based on our model show a cyclic attractor whose configurations can be made to correspond with the current knowledge of the activity of the regulators participating in the gene network during the cell cycle. Additionally, we found two point attractors that can be interpreted in terms of the network configurations directing the two cell types. The entire network is shown to be operating close to the critical regime, which means that it is robust enough to perturbations on dynamics of the network, but adaptable to environmental changes.

Show MeSH
Related in: MedlinePlus