In response to localized imaginal disc damage, Drosophila larvae can alter systemic developmental progression and growth in order to coordinate the regeneration of damaged tissues with the growth and development of undamaged tissues. Previously, we have demonstrated that targeted expression of the TNF homologue eiger, in the wing imaginal discs produces localized apoptosis and tissue damage, and limits the growth of undamaged imaginal discs. However, larval tissue growth is not affected by eiger-induced damage in the wing. In contrast, expression of the pro-apoptotic gene reaper in wing imaginal discs strongly restricts larval growth. reaper-induced damage in the wing is observed in early L1 stage larvae and persists throughout larval development, producing pupae that are significantly smaller than eiger-expressing or control pupae. Therefore, these two distinct apoptotic stimuli produce different non-autonomous effects on larval growth.
To better characterize which apoptotic pathways can produce this non-autonomous larval growth inhibition, we have begun to examine larval growth after the expression of several different apoptotic stimuli. In Drosophila, reaper-induced programmed cell death is critical during development for sculpting final adult tissue shape, deleting pre-adult structures, and regulating cell number. Unlike eiger, which induces apoptosis through JNK signaling, reaper induces apoptosis through direct inhibition of Diap1. We observe that expression of other Diap1 inhibitors hid and grim in the wing discs also causes a strong non-autonomous larval growth inhibition. In contrast, disruption of the wing imaginal disc epithelia by inhibition of the neoplastic tumor suppressor avalanche/Syntaxin-7 does not alter larval growth. Finally, preliminary tests with varied doses of X-irradiation suggest that a subset of irradiated larva may undergo similar growth inhibition. Therefore, the larval growth inhibition resulting from reaper expression in the wing disc is a specific damage response not seen with all apoptotic stimuli. This distinct systemic response may reflect a different mode of tissue repair in response to reaper-induced damage.