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

César Quiñones-Valles,Ismael Sánchez-Osorio,Agustino Martínez-Antonio,Julio Vera

doi:10.1371/journal.pone.0111116

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.

Highlights

Caulobacter crescentus is a model organism used to study cell cycle and differentiation in bacteria [1]
Crescentus and the nature of the regulatory network orchestrating the molecular interactions associated to this differentiation process, it is interesting to investigate how the dynamics of such interactions can reproduce the phenotypes observed in cell division and to what extend the interconnection between regulators and other involved molecules can account for the appearance of the two phenotypes in the bacterium
The model of cell cycle, differentiation and asymmetric cell division in C. crescentus presented here was reconstructed from original literature and considered the assumptions described in previous models

Summary

Introduction

Caulobacter crescentus is a model organism used to study cell cycle and differentiation in bacteria [1]. It is known that this bacterium differentiates and divides asymmetrically generating two phenotypes: the stalked (ST) and swarmer (SW) cell type [2], [3]. G1 is characterized by the differentiation of flagellated swarmer cells to stalked cells During this period, the bacterium ejects the flagellum, retracts the pili, synthesizes the stalk and holdfast structures, and initiates the replication of its DNA [6]. S, called the pre-divisional stage, the DNA is completely replicated and the nucleoids are segregated [7] This early pre-divisional compartmentalization produces differentiated cell poles [8]. The questions that we explore here are: Can the interconnection of the regulatory network and a simple description of its dynamics produce robust oscillatory behavior of the transcription factors during the stages of the cell cycle? How do network interactions generate the two micro-domains and the two cell types in C. crescentus?

Results

Discussion

Conclusion