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The mechanism of cell differentiation in Bacillus subtilis

Abstract

Sporulation in Bacillus subtilis serves as a model for the development of two different cell types from a single cell1. Although much information has been accumulated about the mechanisms that initiate the developmental programmes2, important questions remain that can be answered only by quantitative analysis. Here we develop, with the help of existing and new experimental results, a mathematical model that reproduces published in vitro experiments and explains how the activation of the key transcription factor is regulated. The model identifies the difference in volume between the two cell types as the primary trigger for determining cell fate. It shows that this effect depends on the allosteric behaviour of a key protein kinase and on a low rate of dephosphorylation by the corresponding phosphatase; both predicted effects are confirmed experimentally.

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Figure 1: Regulation of σ F release during sporulation.
Figure 2: SpoIIAB is an allosteric protein.
Figure 3: Verification of the model with in vitro data.
Figure 4: Mechanism of prespore-specific σ F –RNA-polymerase holoenzyme formation.

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Acknowledgements

We thank J.-C. Shu for providing unpublished SPR and AA phosphorylation data. This work was supported by the BBSRC UK. D.I. is a Junior Research Fellow at St John's College, Oxford, and is supported by a EPSRC DTA studentship. I.D.C. acknowledges financial support from the Wellcome Trust and the NIH-funded Cell Migration Consortium. Author Contributions D.I. developed the model and conducted the simulations. J.C. performed the experiments and all the authors contributed to the concepts and writing of the paper.

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Correspondence to Dagmar Iber or Michael D. Yudkin.

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Supplementary Notes

This file contains details on the derivation of the mathematical model and of parameter values and a discussion of the wider relevance of the model. The also contains Supplementary Figures 1–12 and Supplementary Tables 1–3. (PDF 762 kb)

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Iber, D., Clarkson, J., Yudkin, M. et al. The mechanism of cell differentiation in Bacillus subtilis. Nature 441, 371–374 (2006). https://doi.org/10.1038/nature04666

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