Understanding cell migration is centrally important to modern cell biology. However, despite years of study, progress has been hindered by experimental limitations and the complexity of the process. This has led to the popularity of Dictyostelium discoideum, with its experimentally-friendly lifestyle and small, haploid genome, as a tool to dissect the pathways involved in migration. This humble amoeba is now established at the centre of dramatic changes in our understanding of cell movement. In this review we describe the recent reinterpretation of the role of phosphatidlylinositol trisphosphate (PIP3) and other intracellular messengers that connect signalling and migration, and the transition to models of chemotaxis driven by multiple, intertwined signalling pathways. In shallow gradients, pseudopods are generated with random directions, and we discuss how chemotaxis can operate by biasing this process. Overall we describe how Dictyostelium has the potential to unlock many fundamental questions in the cell motility field.
