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

cAMP followers The slime mould Dictyostelium discoideum is popular with cell biologists as a model for a multicellular way of life. When food is short its free-living soil amoebae aggregate to form a multicellular body that differentiates and produces spores. Work by Gerisch and others in the 1970s showed that aggregation is controlled by pulses of cyclic AMP, and now experiments with mutants lacking cAMP-dependent protein kinase A show how this system works. Cells communicate via a cAMP signal relay to create outwardly propagating waves of cAMP that control inward movement of cells. Numerical models suggests that self-organization is fine-tuned by a genetic circuit acting via protein kinase A to create an overall wave pattern; in its absence a series of unconnected spiral cores develops. Other systems, such as heart muscle, may act similarly to suppress deleterious spiral waves. 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 waves 1 , 2 , 3 , 4 that self-organize in a homogeneous cell population. Spiral waves are ubiquitously observed in chemical reactions as well as in biological systems 5 , 6 , 7 , 8 . Although feedback control of spiral waves in spatially extended chemical reactions has been demonstrated in recent years 9 , 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.