Signalling during dictyostelium development

Abstract

Dictyostelium has become an important model system to study the molecular details of the signalling pathways controlling gradient sensing and cell polarisation that control localised activation of the actin-myosin cytoskeleton responsible for evolutionary highly conserved mechanisms of chemotactic cell movement up chemoattractant gradients. 3′-5′ cyclic AMP is the chemoattractant that controls the chemotactic cell movements that result in aggregation of up to several hundred thousand cells, slug formation, migration and fruiting body formation. The coordination of these complex cell movements require long-range cAMP mediated cell-cell signalling based on periodic initiation of cAMP signals in the aggregation centre and slug tip and relay by surrounding cells, resulting in highly dynamic patterns of cAMP wave propagation. Model calculations have shown that the dynamic feedbacks between autocatalytic cell-cell cAMP signalling and cAMP-mediated collective chemotactic cell movement result in emergent properties that readily explain multicellular morphogenesis. cAMP signalling not only controls cell movement but also acts as a key morphogen to control cell differentiation, which in turn affects cell type specific cell-cell signalling and cell movement, adding an additional layer of feedback. To fully understand the multicellular morphogenesis of this organism at the level of cell behaviours, it will be needed to integrate the detailed cell type proportioning mechanisms in models describing cell-cell signalling and movement. Dictyostelium is likely to be the first eukaryotic organism where it will be possible to quantitatively understand how multicellular development and morphogenesis arise as emergent properties from a few relatively simple collective cell behaviours.