Fig. P1.

The diagram summarizes the design and outcomes of experiments aimed at understanding why ATM mutations cause neurodegeneration in humans. In the adult fly brain, ATM was genetically manipulated in three ways, and the outcomes were monitored in neurons and glial cells. Reduced ATM level only in neurons did not cause neuron or glial cell death, represented by a smiley face. In contrast, reduced ATM kinase activity in all cells or reduced ATM level only in glial cells caused neuron and glial cell death, represented by a skull-and-crossbones symbol. Additionally, reduced ATM kinase activity in all cells or reduced ATM level only in glial cells caused activation of the innate immune response (IIR) in glial cells and increased expression of immune molecules, such as AMPs (colored circles). The effect of secreted AMPs on neurons is not known and is thus represented by a question mark.