TY - JOUR

T1 - Drosophila Lgr3 Couples Organ Growth with Maturation and Ensures Developmental Stability

AU - Colombani, Julien

AU - Andersen, Ditte S

AU - Boulan, Laura

AU - Boone, Emilie

AU - Romero, Nuria

AU - Virolle, Virginie

AU - Texada, Michael

AU - Léopold, Pierre

N1 - Copyright © 2015 Elsevier Ltd. All rights reserved.

PY - 2015/10/19

Y1 - 2015/10/19

N2 - 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.

AB - 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.

KW - Animals

KW - Brain/physiology

KW - Drosophila Proteins/genetics

KW - Drosophila melanogaster/genetics

KW - Gene Expression Regulation, Developmental

KW - Intercellular Signaling Peptides and Proteins/genetics

KW - Larva/genetics

KW - Neurons/metabolism

KW - Organ Size

KW - Receptors, G-Protein-Coupled/genetics

KW - Signal Transduction

U2 - 10.1016/j.cub.2015.09.020

DO - 10.1016/j.cub.2015.09.020

M3 - Journal article

C2 - 26441350

VL - 25

SP - 2723

EP - 2729

JO - Current Biology

JF - Current Biology

SN - 0960-9822

IS - 20

ER -