Eyeless uncouples mushroom body neuroblast proliferation from dietary amino acids in Drosophila

Elife. 2017 Aug 9;6:e26343. doi: 10.7554/eLife.26343.


Cell proliferation is coupled with nutrient availability. If nutrients become limited, proliferation ceases, because growth factor and/or PI3-kinase activity levels become attenuated. Here, we report an exception to this generality within a subpopulation of Drosophila neural stem cells (neuroblasts). We find that most neuroblasts enter and exit cell cycle in a nutrient-dependent manner that is reversible and regulated by PI3-kinase. However, a small subset, the mushroom body neuroblasts, which generate neurons important for memory and learning, divide independent of dietary nutrient conditions and PI3-kinase activity. This nutrient-independent proliferation is regulated by Eyeless, a Pax-6 orthologue, expressed in mushroom body neuroblasts. When Eyeless is knocked down, mushroom body neuroblasts exit cell cycle when nutrients are withdrawn. Conversely, when Eyeless is ectopically expressed, some non-mushroom body neuroblasts divide independent of dietary nutrient conditions. Therefore, Eyeless uncouples MB neuroblast proliferation from nutrient availability, allowing preferential neurogenesis in brain subregions during nutrient poor conditions.

Keywords: D. melanogaster; PI3-kinase; Pax-6; developmental biology; diet; eyeless; neural stem cell; neuroblast; stem cells.

MeSH terms

  • Amino Acids / metabolism*
  • Animals
  • Brain / cytology
  • Brain / growth & development
  • Brain / metabolism
  • Cell Cycle / genetics
  • Cell Proliferation
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism
  • Eating / physiology
  • Gene Expression Regulation, Developmental
  • Memory / physiology
  • Mushroom Bodies / cytology
  • Mushroom Bodies / growth & development
  • Mushroom Bodies / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism*
  • Neurogenesis / genetics*
  • Neurons / cytology
  • Neurons / metabolism
  • Phosphatidylinositol 3-Kinases / genetics*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction


  • Amino Acids
  • DNA-Binding Proteins
  • Drosophila Proteins
  • ey protein, Drosophila
  • Phosphatidylinositol 3-Kinases