PMID- 26441350
OWN - NLM
STAT- MEDLINE
DCOM- 20160804
LR  - 20151021
IS  - 1879-0445 (Electronic)
IS  - 0960-9822 (Linking)
VI  - 25
IP  - 20
DP  - 2015 Oct 19
TI  - Drosophila Lgr3 Couples Organ Growth with Maturation and Ensures Developmental 
      Stability.
PG  - 2723-9
LID - S0960-9822(15)01099-4 [pii]
LID - 10.1016/j.cub.2015.09.020 [doi]
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.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Colombani, Julien
AU  - Colombani J
AD  - 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.
FAU - Andersen, Ditte S
AU  - Andersen DS
AD  - 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.
FAU - Boulan, Laura
AU  - Boulan L
AD  - 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.
FAU - Boone, Emilie
AU  - Boone E
AD  - 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.
FAU - Romero, Nuria
AU  - Romero N
AD  - 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.
FAU - Virolle, Virginie
AU  - Virolle V
AD  - 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.
FAU - Texada, Michael
AU  - Texada M
AD  - HHMI Janelia Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
FAU - Leopold, Pierre
AU  - Leopold P
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151001
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Drosophila Proteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Lgr3 protein, Drosophila)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (insulin-like peptide 8, Drosophila)
SB  - IM
MH  - Animals
MH  - Brain/physiology
MH  - Drosophila Proteins/*genetics/metabolism
MH  - Drosophila melanogaster/*genetics/growth & development/metabolism
MH  - *Gene Expression Regulation, Developmental
MH  - Intercellular Signaling Peptides and Proteins/*genetics/metabolism
MH  - Larva/genetics/growth & development/metabolism
MH  - Neurons/metabolism
MH  - Organ Size
MH  - Receptors, G-Protein-Coupled/*genetics/metabolism
MH  - Signal Transduction
EDAT- 2015/10/07 06:00
MHDA- 2016/08/05 06:00
CRDT- 2015/10/07 06:00
PHST- 2015/06/22 00:00 [received]
PHST- 2015/08/21 00:00 [revised]
PHST- 2015/09/08 00:00 [accepted]
PHST- 2015/10/07 06:00 [entrez]
PHST- 2015/10/07 06:00 [pubmed]
PHST- 2016/08/05 06:00 [medline]
AID - S0960-9822(15)01099-4 [pii]
AID - 10.1016/j.cub.2015.09.020 [doi]
PST - ppublish
SO  - Curr Biol. 2015 Oct 19;25(20):2723-9. doi: 10.1016/j.cub.2015.09.020. Epub 2015 
      Oct 1.