Regeneration and tissue repair is a fascinating process that allows organisms to maintain homeostasis after tissue injury. Molecular mechanisms for tissue repair and regeneration within damaged tissue have been extensively studied. However, the systemic regulation of tissue repair remains poorly understood. To elucidate tissue nonautonomous control of repair process, it is essential to manipulate genes in uninjured parts of the body, independent of local tissue damage.
In this study, we develop a system in Drosophila for spatiotemporal tissue injury using a temperature-sensitive form of Diphtheria toxin A domain (DtAts) driven by the Q system to study factors contributing to imaginal disc repair. This system enables us to induce reproducible tissue damage and to perform genetic screening with Gal4 system in uninjured tissues. Using this system, we demonstrate that methionine metabolism in the fat body, a counterpart of mammalian liver and adipose tissue, supports the repair processes of wing discs. Local injury to wing discs decreases methionine (Met) and S-adenosylmethionine (SAM), whereas it increases S-adenosylhomocysteine (SAH) in the fat body, implying that SAM consumption is increased at the early stage of tissue repair. Fat body-specific genetic manipulation of methionine metabolism results in defective disc repair, but does not affect normal wing development. These results indicate the contribution of tissue interactions to tissue repair in Drosophila, as local damage to wing discs influences fat body metabolism, and proper regulation of methionine metabolism in the fat body, in turn, affects disc repair.