Genes and pathways governing D. discoideum vacuolar cell death. The cascade of subcellular cell death events is schematically depicted (middle). These include the formation of “paddle” cells, following by their rounding, biogenesis of a cellulose shell and extensive vacuolization. Random insertional mutagenesis and targeted mutagenesis identified a number of genes, here shown in green letters, encoding molecules required for this cell death. Details are given in the main text. These genes in turn helped define pathways to cell death, such as a polysaccharide pathway (right), a first signal pathway induced by starvation and cAMP (lower left) and second signal pathways (upper left). The latter include a DIF-1-induced autonomous pathway and a c-di-GMP pathway requiring endogenously synthesized or exogenous DIF-1. Ca2+-related drugs such as thapsigargin and BAPTA affect DIF-1 signaling leading to cell death.