Growth is coordinated during regeneration through the regulation of ecdysone by Dilp8 via nitric oxide signaling. Jacob Jaszczak, Anh Dao, Adrian Halme. Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA.

   During development, coordination of organ growth produces animals of normal size and proportion. In Drosophila, localized imaginal disc damage initiates a regenerative response in damaged tissues and attenuates the growth of undamaged imaginal discs. The growth inhibition in undamaged tissues may function to coordinate regeneration with developmental growth. In contrast to the imaginal tissues, we show larval tissues to not experience similar growth restriction following imaginal disc damage; it is not likely that growth of undamaged imaginal discs is reduced by inhibiting global insulin signaling. Nitric oxide synthase (NOS) functions in systemic immune responses and growth inhibition. We examined NOS function during systemic growth coordination following localized imaginal disc damage, and show NOS to be necessary and sufficient for attenuating growth of undamaged imaginal discs. During localized tissue damage and regeneration, NOS activity is increased in the prothoracic gland (PG). NOS overexpression in the PG is sufficient to attenuate growth in imaginal discs and produces a substantial developmental delay. Both the growth and delay phenotypes can be suppressed by exogenous ecdysone, suggesting that NOS activity in the PG suppresses ecdysone synthesis. Previous experiments (Caceres et al. 2011) show that NOS activity in the PG of post-feeding larvae promotes the expression of ecdysone biosynthesis genes and ecdysone synthesis. In contrast, our experiments in earlier third-instar larvae suggest that NOS activity in the PG may have the opposite effect on ecdysone synthesis; NOS functions to decrease ecdysone signaling, thereby coordinating regenerative and developmental growth. Additionally, we show that NOS activity is increased in the PG when Dilp8 is expressed in wing imaginal discs. These results suggest that NOS activity in the PG may mediate the effects of Dilp8 and ecdysone, coordinating growth and developmental timing during regeneration.