title: Growth Coordination During Drosophila melanogaster Imaginal Disc Regeneration Is Mediated by Signaling Through the Relaxin Receptor Lgr3 in the Prothoracic Gland.
abstract: Damage to Drosophila melanogaster imaginal discs activates a regeneration checkpoint that (1) extends larval development and (2) coordinates the regeneration of the damaged disc with the growth of undamaged discs. These two systemic responses to damage are both mediated by Dilp8, a member of the insulin/insulin-like growth factor/relaxin family of peptide hormones, which is released by regenerating imaginal discs. Growth coordination between regenerating and undamaged imaginal discs is dependent on Dilp8 activation of nitric oxide synthase (NOS) in the prothoracic gland (PG), which slows the growth of undamaged discs by limiting ecdysone synthesis. Here we demonstrate that the Drosophila relaxin receptor homolog Lgr3, a leucine-rich repeat-containing G-protein-coupled receptor, is required for Dilp8-dependent growth coordination and developmental delay during the regeneration checkpoint. Lgr3 regulates these responses to damage via distinct mechanisms in different tissues. Using tissue-specific RNA-interference disruption of Lgr3 expression, we show that Lgr3 functions in the PG upstream of NOS, and is necessary for NOS activation and growth coordination during the regeneration checkpoint. When Lgr3 is depleted from neurons, imaginal disc damage no longer produces either developmental delay or growth inhibition. To reconcile these discrete tissue requirements for Lgr3 during regenerative growth coordination, we demonstrate that Lgr3 activity in both the CNS and PG is necessary for NOS activation in the PG following damage. Together, these results identify new roles for a relaxin receptor in mediating damage signaling to regulate growth and developmental timing.
authors: Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, Virginia 22908.
authors: Jacob S
authors: JS
authors: Jaszczak
authors: Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, Virginia 22908.
authors: Jacob B
authors: JB
authors: Wolpe
authors: Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, Virginia 22908.
authors: Rajan
authors: R
authors: Bhandari
authors: Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, Virginia 22908.
authors: Rebecca G
authors: RG
authors: Jaszczak
authors: Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, Virginia 22908 ajh6a@virginia.edu.
authors: Adrian
authors: http://orcid.org/0000-0002-6608-5305
authors: A
authors: Halme
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development; D004440:Ecdysone / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D060227:Imaginal Discs / Q000254:growth & development* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007814:Larva / Q000254:growth & development; D009474:Neurons / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012038:Regeneration / Q000235:genetics; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000603337:Lgr3 protein, Drosophila; D016601:RNA-Binding Proteins; D043562:Receptors, G-Protein-Coupled; C572149:insulin-like peptide 8, Drosophila; C070574:nos protein, Drosophila; D004440:Ecdysone
keywords: Lgr3; checkpoint; growth coordination; regeneration