A Brain Circuit That Synchronizes Growth and Maturation Revealed Through Dilp8 Binding to Lgr3

Science. 2015 Nov 13;350(6262):aac6767. doi: 10.1126/science.aac6767. Epub 2015 Oct 1.


Body-size constancy and symmetry are signs of developmental stability. Yet, it is unclear exactly how developing animals buffer size variation. Drosophila insulin-like peptide Dilp8 is responsive to growth perturbations and controls homeostatic mechanisms that coordinately adjust growth and maturation to maintain size within the normal range. Here we show that Lgr3 is a Dilp8 receptor. Through the use of functional and adenosine 3',5'-monophosphate assays, we defined a pair of Lgr3 neurons that mediate homeostatic regulation. These neurons have extensive axonal arborizations, and genetic and green fluorescent protein reconstitution across synaptic partners show that these neurons connect with the insulin-producing cells and prothoracicotropic hormone-producing neurons to attenuate growth and maturation. This previously unrecognized circuit suggests how growth and maturation rate are matched and co-regulated according to Dilp8 signals to stabilize organismal size.

Publication types

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

MeSH terms

  • Adenosine Monophosphate / metabolism
  • Animals
  • Body Size
  • Brain / cytology
  • Brain / growth & development*
  • Brain / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / growth & development*
  • Drosophila melanogaster / metabolism
  • Homeostasis
  • Insect Hormones / genetics
  • Insect Hormones / metabolism
  • Insulin / metabolism*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Nerve Net / cytology
  • Nerve Net / metabolism
  • Neurons / metabolism*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Peptide / genetics
  • Receptors, Peptide / metabolism*
  • Signal Transduction
  • Synapses / metabolism


  • Drosophila Proteins
  • Insect Hormones
  • Insulin
  • Intercellular Signaling Peptides and Proteins
  • Lgr3 protein, Drosophila
  • Receptors, G-Protein-Coupled
  • Receptors, Peptide
  • insulin-like peptide 8, Drosophila
  • relaxin receptors
  • Adenosine Monophosphate
  • prothoracicotropic hormone