Dilp8 requires the neuronal relaxin receptor Lgr3 to couple growth to developmental timing

Nat Commun. 2015 Oct 29;6:8732. doi: 10.1038/ncomms9732.

Abstract

How different organs in the body sense growth perturbations in distant tissues to coordinate their size during development is poorly understood. Here we mutate an invertebrate orphan relaxin receptor gene, the Drosophila Leucine-rich repeat-containing G protein-coupled receptor 3 (Lgr3), and find body asymmetries similar to those found in insulin-like peptide 8 (dilp8) mutants, which fail to coordinate growth with developmental timing. Indeed, mutation or RNA intereference (RNAi) against Lgr3 suppresses the delay in pupariation induced by imaginal disc growth perturbation or ectopic Dilp8 expression. By tagging endogenous Lgr3 and performing cell type-specific RNAi, we map this Lgr3 activity to a new subset of CNS neurons, four of which are a pair of bilateral pars intercerebralis Lgr3-positive (PIL) neurons that respond specifically to ectopic Dilp8 by increasing cAMP-dependent signalling. Our work sheds new light on the function and evolution of relaxin receptors and reveals a novel neuroendocrine circuit responsive to growth aberrations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / growth & development*
  • Brain / metabolism
  • Cyclic AMP / metabolism
  • Drosophila / genetics
  • Drosophila / growth & development
  • Drosophila / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Female
  • Gene Expression Regulation, Developmental
  • Imaginal Discs / growth & development
  • Imaginal Discs / metabolism
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Molecular Sequence Data
  • Neurons / metabolism*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Relaxin / metabolism
  • Signal Transduction

Substances

  • Drosophila Proteins
  • Intercellular Signaling Peptides and Proteins
  • Lgr3 protein, Drosophila
  • Receptors, G-Protein-Coupled
  • insulin-like peptide 8, Drosophila
  • Relaxin
  • Cyclic AMP

Associated data

  • GENBANK/KT321103
  • GENBANK/KT321104
  • GENBANK/KT321105
  • GENBANK/KT321106
  • GENBANK/KT321107
  • GENBANK/KT321108
  • GENBANK/KT321109
  • GENBANK/KT321110
  • GENBANK/KT321111
  • GENBANK/KT321112
  • GENBANK/KT321113