Combining experiments and modelling to understand size regulation in Dictyostelium discoideum

Little is known about how the sizes of specific organs and tissues are regulated. To try to understand these mechanisms, we have been using a combination of modelling and experiments to study the simple system Dictyostelium discoideum, which forms approximately 20000 cell groups. We found that cells secrete a factor, and as the number of cells increases, the concentration of the factor increases. Diffusion calculations indicated that this lets cells sense the local cell density. Computer simulations predicted, and experiments then showed, that this factor decreases cell-cell adhesion and increases random cell motility. In a group, adhesion forces keep cells together, while random motility forces cause cells to pull apart and separate from each other. As the group size increases above a threshold, the factor concentration goes above a threshold and the cells switch from an adhered state to a separated state. This causes excessively large groups to break apart and/or dissipate, creating an upper limit to group size. In this review, we focus on how computer simulations made testable predictions that led the way to understanding the size regulation mechanism mediated by this factor.