Nitric Oxide Synthase Mediates Growth Coordination During Drosophila Melanogaster Imaginal Disc Regeneration

Regulation of developmental growth is necessary to form animals of specific size and proportion. Growth coordination between organs ensures that each organ develops to the right size and proportion. The mechanisms regulating the coordination of developmental growth are not fully understood. Using Drosophila melanogaster regeneration as a model for developmental growth coordination, I describe a novel pathway through which tissues communicate with a central endocrine organ, the prothoracic gland, to coordinate growth. During Drosophila larval development, damage to imaginal discs activates a regeneration checkpoint that slows the growth of undamaged imaginal discs, coordinating regeneration of the damaged discs with developmental growth. Drosophila insulin-like peptide 8 (Dilp8) is secreted from regenerating imaginal discs and restricts growth of the undamaged imaginal discs. I identify nitric oxide synthase (NOS) as a target of Dilp8 signaling. During regeneration, Dilp8 activates NOS signaling in the prothoracic gland, reducing ecdysone biosynthesis to slow the growth of undamaged tissues. I also identify Lgr3 as a putative receptor for Dilp8. Lgr3 mediates growth coordination and regulates NOS signaling in the PG. Additionally, Dilp8 and Lgr3 also regulate bilateral symmetry in Drosophila and Lgr3 regulates organ-proportions in mammals. This suggests that the Dilp8-Lgr3- NOS pathway, which regulates organ growth through signaling in the endocrine system, may be conserved beyond Drosophila regeneration.