Tre1 GPCR signaling orients stem cell divisions in the Drosophila central nervous system

Dev Cell. 2012 Jan 17;22(1):79-91. doi: 10.1016/j.devcel.2011.10.027. Epub 2011 Dec 15.


During development, directional cell division is a major mechanism for establishing the orientation of tissue growth. Drosophila neuroblasts undergo asymmetric divisions perpendicular to the overlying epithelium to produce descendant neurons on the opposite side, thereby orienting initial neural tissue growth. However, the mechanism remains elusive. We provide genetic evidence that extrinsic GPCR signaling determines the orientation of cortical polarity underlying asymmetric divisions of neuroblasts relative to the epithelium. The GPCR Tre1 activates the G protein oα subunit in neuroblasts by interacting with the epithelium to recruit Pins, which regulates spindle orientation. Because Pins associates with the Par-complex via Inscuteable, Tre1 consequently recruits the polarity complex to orthogonally orient the polarity axis to the epithelium. Given the universal role of the Par complex in cellular polarization, we propose that the GPCR-Pins system is a comprehensive mechanism controlling tissue polarity by orienting polarized stem cells and their divisions.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Division / physiology*
  • Cell Polarity*
  • Cells, Cultured
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development*
  • Drosophila melanogaster / metabolism*
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism
  • GTP-Binding Protein alpha Subunits / genetics
  • GTP-Binding Protein alpha Subunits / metabolism
  • Immunoenzyme Techniques
  • Immunoprecipitation
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Neurons / cytology*
  • Neurons / metabolism
  • Peptidylprolyl Isomerase / genetics
  • Peptidylprolyl Isomerase / metabolism
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction
  • Spindle Apparatus
  • Stem Cells / cytology*
  • Stem Cells / metabolism


  • Drosophila Proteins
  • GTP-Binding Protein alpha Subunits
  • NIMA-Interacting Peptidylprolyl Isomerase
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Tre1 protein, Drosophila
  • Peptidylprolyl Isomerase
  • dod protein, Drosophila