title: Drosophila Lgr3 Couples Organ Growth with Maturation and Ensures Developmental Stability.
abstract: Early transplantation and grafting experiments suggest that body organs follow autonomous growth programs [1-3], therefore pointing to a need for coordination mechanisms to produce fit individuals with proper proportions. We recently identified Drosophila insulin-like peptide 8 (Dilp8) as a relaxin and insulin-like molecule secreted from growing tissues that plays a central role in coordinating growth between organs and coupling organ growth with animal maturation [4, 5]. Deciphering the function of Dilp8 in growth coordination relies on the identification of the receptor and tissues relaying Dilp8 signaling. We show here that the orphan receptor leucine-rich repeat-containing G protein-coupled receptor 3 (Lgr3), a member of the highly conserved family of relaxin family peptide receptors (RXFPs), mediates the checkpoint function of Dilp8 for entry into maturation. We functionally identify two Lgr3-positive neurons in each brain lobe that are required to induce a developmental delay upon overexpression of Dilp8. These neurons are located in the pars intercerebralis, an important neuroendocrine area in the brain, and make physical contacts with the PTTH neurons that ultimately control the production and release of the molting steroid ecdysone. Reducing Lgr3 levels in these neurons results in adult flies exhibiting increased fluctuating bilateral asymmetry, therefore recapitulating the phenotype of dilp8 mutants. Our work reveals a novel Dilp8/Lgr3 neuronal circuitry involved in a feedback mechanism that ensures coordination between organ growth and developmental transitions and prevents developmental variability.
authors.affiliation: University of Nice-Sophia Antipolis, Institute of Biology Valrose, 06108 Nice, France; CNRS, Institute of Biology Valrose, 06108 Nice, France; INSERM, Institute of Biology Valrose, 06108 Nice, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Colombani
authors.affiliation: University of Nice-Sophia Antipolis, Institute of Biology Valrose, 06108 Nice, France; CNRS, Institute of Biology Valrose, 06108 Nice, France; INSERM, Institute of Biology Valrose, 06108 Nice, France. Electronic address: ditte.andersen@unice.fr.
authors.forename: Ditte S
authors.initials: DS
authors.lastname: Andersen
authors.affiliation: University of Nice-Sophia Antipolis, Institute of Biology Valrose, 06108 Nice, France; CNRS, Institute of Biology Valrose, 06108 Nice, France; INSERM, Institute of Biology Valrose, 06108 Nice, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Boulan
authors.affiliation: University of Nice-Sophia Antipolis, Institute of Biology Valrose, 06108 Nice, France; CNRS, Institute of Biology Valrose, 06108 Nice, France; INSERM, Institute of Biology Valrose, 06108 Nice, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Boone
authors.affiliation: University of Nice-Sophia Antipolis, Institute of Biology Valrose, 06108 Nice, France; CNRS, Institute of Biology Valrose, 06108 Nice, France; INSERM, Institute of Biology Valrose, 06108 Nice, France.
authors.forename: Nuria
authors.initials: N
authors.lastname: Romero
authors.affiliation: University of Nice-Sophia Antipolis, Institute of Biology Valrose, 06108 Nice, France; CNRS, Institute of Biology Valrose, 06108 Nice, France; INSERM, Institute of Biology Valrose, 06108 Nice, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Virolle
authors.affiliation: HHMI Janelia Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Texada
authors.affiliation: University of Nice-Sophia Antipolis, Institute of Biology Valrose, 06108 Nice, France; CNRS, Institute of Biology Valrose, 06108 Nice, France; INSERM, Institute of Biology Valrose, 06108 Nice, France. Electronic address: leopold@unice.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Léopold
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009929:Organ Size; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000603337:Lgr3 protein, Drosophila; D043562:Receptors, G-Protein-Coupled; C572149:insulin-like peptide 8, Drosophila