Insulin receptor-mediated signaling via phospholipase C-γ regulates growth and differentiation in Drosophila

PLoS One. 2011;6(11):e28067. doi: 10.1371/journal.pone.0028067. Epub 2011 Nov 21.

Abstract

Coordination between growth and patterning/differentiation is critical if appropriate final organ structure and size is to be achieved. Understanding how these two processes are regulated is therefore a fundamental and as yet incompletely answered question. Here we show through genetic analysis that the phospholipase C-γ (PLC-γ) encoded by small wing (sl) acts as such a link between growth and patterning/differentiation by modulating some MAPK outputs once activated by the insulin pathway; particularly, sl promotes growth and suppresses ectopic differentiation in the developing eye and wing, allowing cells to attain a normal size and differentiate properly. sl mutants have previously been shown to have a combination of both growth and patterning/differentiation phenotypes: small wings, ectopic wing veins, and extra R7 photoreceptor cells. We show here that PLC-γ activated by the insulin pathway participates broadly and positively during cell growth modulating EGF pathway activity, whereas in cell differentiation PLC-γ activated by the insulin receptor negatively regulates the EGF pathway. These roles require different SH2 domains of PLC-γ, and act via classic PLC-γ signaling and EGF ligand processing. By means of PLC-γ, the insulin receptor therefore modulates differentiation as well as growth. Overall, our results provide evidence that PLC-γ acts during development at a time when growth ends and differentiation begins, and is important for proper coordination of these two processes.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation*
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / growth & development*
  • Drosophila melanogaster / ultrastructure
  • Eye / anatomy & histology
  • Eye / cytology
  • Eye / ultrastructure
  • Female
  • Gene Dosage / genetics
  • Genes, Insect / genetics
  • MAP Kinase Signaling System / genetics
  • Models, Biological
  • Mutation / genetics
  • Organ Size
  • Phenotype
  • Phospholipase C gamma / chemistry
  • Phospholipase C gamma / metabolism*
  • Photoreceptor Cells, Invertebrate / metabolism
  • Protein Structure, Tertiary
  • Receptor, Insulin / metabolism*
  • Signal Transduction* / genetics
  • Wings, Animal / cytology
  • Wings, Animal / enzymology
  • Wings, Animal / growth & development

Substances

  • Drosophila Proteins
  • Receptor, Insulin
  • Phospholipase C gamma
  • SL protein, Drosophila