(A) Introduction of the pro-apoptotic protein Hid into the posterior compartment (left) of the Drosophila wing imaginal disc triggers the propagation of apoptosis from the posterior to the anterior (right) compartment; introducing a protein called Reaper has a similar effect. The presence of Hid or Reaper in the posterior cells triggers the apoptotic loop: it degrades the anti-apoptotic protein Diap1, thus allowing activation of the caspase Dronc. This has two consequences: it activates the caspase Drice, which is responsible for actually killing the cell, and it upregulates the JNK pathway, which amplifies the activity of the genes that code for Hid and Reaper. The posterior cells produce a ligand called Eiger (Egr), which diffuses across the anterior–posterior border and activates the JNK pathway in anterior cells, triggering apoptosis. It is thought that the Eiger signal is produced by the JNK pathway itself, but the evidence is not conclusive (hence the question mark). (B) Schematic representation of AiA. The cells at the focal point of the initial apoptotic event emit death signals: Egr in flies or TNF-α in mammals. These signals diffuse away and induce secondary apoptosis in cells located at a distance from the primary focus. (C–E) are examples of scenarios in which AiA may play a role—these include normal processes such as the hair follicle cycle (C), pathological situations such as heart infarction (D), as well as radiation therapy in tumours (E).