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An autoregulatory circuit for long-range self-organization in Dictyostelium cell populations


Nutrient-deprived Dictyostelium amoebae aggregate to form a multicellular structure by chemotaxis, moving towards propagating waves of cyclic AMP that are relayed from cell to cell. Organizing centres are not formed by founder cells, but are dynamic entities consisting of cores of outwardly rotating spiral waves1,2,3,4 that self-organize in a homogeneous cell population. Spiral waves are ubiquitously observed in chemical reactions as well as in biological systems5,6,7,8. Although feedback control of spiral waves in spatially extended chemical reactions has been demonstrated in recent years9,10, the mechanism by which control is achieved in living systems is unknown. Here we show that mutants of the cyclic AMP/protein kinase A pathway show periodic signalling, but fail to organize coherent long-range wave territories, owing to the appearance of numerous spiral cores. A theoretical model suggests that autoregulation of cell excitability mediated by protein kinase A acts to optimize the number of signalling centres.

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Figure 1: Mutants in the PKA circuit show spatially aberrant wave patterns.
Figure 2: Time evolution of signalling is greatly altered in the mutants.
Figure 3: Time delay embedding and the extraction of spatial phase singularities8 reveals the unusual number of spiral cores in the mutants (see Supplementary Methods, Video S2 and Fig. S4).
Figure 4: Cellular automaton simulations and resulting waveforms.


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The authors thank X. J. Guan and other members of the Cox laboratory for assistance, J. E. Segall for HS174 and HS174-A1, A. Kuspa for AK1045, H. Kuwayama for the pkaC-null strain, A. Harwood for the pka-Rm and Rc expression vectors, M. Veron for the anti-PKA-R monoclonal antibody, J. T. Bonner and M. Sano for discussions and K. McQuade, R. Segev and G. Weeks for detailed comments on our earlier manuscript. The authors also thank the Dictyostelium Stock Centre for providing HTY506. P.A.T. received a fellowship from the Wellcome Trust. This work was supported by a grant to E.C.C. from the NIH.

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Correspondence to Satoshi Sawai or Edward C. Cox.

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Supplementary information

Supplementary Notes

This file contains the legends for Supplementary Figures S4 and S5, Supplementary Discussion, Supplementary Equations, Supplementary Methods and additional references. (DOC 88 kb)

Supplementary Movie 1

This movie is a time-lapse recording of the optical density waves shown in Fig. 1b. Each panel is 29 mm 2 29 mm. The time label is added only to show the frame speed of the movie and does not represent the time elapsed after starvation. The movie clip is edited so that each panel starts 4-5 h after starvation. The movie of the erkB mutant starts approximately 10 h after starvation. (MPG 2130 kb)

Supplementary Movie 2

This movie shows the angular variable representation of the optical density waves and phase singularities (snapshots shown in Fig. 3a and Supplementary Fig. S4). Each panel is 12 mm 2 12 mm. The frame speed is the same as Supplementary Movie 1. (MPG 2423 kb)

Supplementary Movie 3

This movie shows the effect of starvation treatment on waveform and the simulations using initial conditions with higher excitability (Fig. 4 c-f). (MPG 5534 kb)

Supplementary Figure S4

A time-delay embedding technique reveals abnormal numbers of phase singularities in the mutants. (PDF 664 kb)

Supplementary Figure S5

Application of a mist of cAMP resets the phase of the optical density oscillations in the field of erkB mutants. (PDF 740 kb)

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Sawai, S., Thomason, P. & Cox, E. An autoregulatory circuit for long-range self-organization in Dictyostelium cell populations. Nature 433, 323–326 (2005).

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