Tissue damage results in a series of responses, not only locally but also systemically in distant tissues. We call this response as systemic damage response (SDR) in contrast to local damage response (LDR). To study the involvement of SDR in tissue regeneration context, we applied genetic tools to manipulate genes in two different tissues independently in Drosophila. We performed spatiotemporal injury of wing imaginal discs using a temperature-sensitive form of Diphtheria toxin A domain (DtAts) driven by the Q system. Metabolome analysis revealed that local injury to wing imaginal discs decreases methionine (Met) and its first metabolite S-adenosylmethionine (SAM) in hemolymph and fat body. Fat body-specific manipulation of Met metabolism genes by Ga4/UAS system results in defective wing disc repair. These results indicate the contribution of tissue interactions to tissue repair in Drosophila, as local damage to wing imaginal discs influences fat body SAM metabolism as SDR, and proper control of SAM metabolism in the fat body regulates wing disc repair and regeneration.
The damaged Drosophila adult gut epithelia is renewed by intestinal stem cell (ISC). Gut is a primary tissue that faces ingested nutrients, therefore it is an in vivo elegant model for studying nutrient control of tissue regeneration. Under Met-depleted food condition, proliferation of ISC was significantly suppressed. Genetic analysis revealed that SAM reduction in ISC leads the alteration of translation and proliferation of the ISC. In contrast, SAM depletion induces upd3 up-regulation in the enterocytes, nutrient absorption cells in the gut. The up-regulated Upd3 is required for rapid ISC proliferation after refeeding. Therefore, SAM governs cell type specific response for maintaining gut homeostasis under starvation.