FOXO/Fringe is necessary for maintenance of the germline stem cell niche in response to insulin insufficiency

Dev Biol. 2013 Oct 1;382(1):124-35. doi: 10.1016/j.ydbio.2013.07.018. Epub 2013 Jul 27.


The stem cell niche houses and regulates stem cells by providing both physical contact and local factors that regulate stem cell identity. The stem cell niche also plays a role in integrating niche-local and systemic signals, thereby ensuring that the balance of stem cells meets the needs of the organism. However, it is not clear how these signals are merged within the niche. Nutrient-sensing insulin/FOXO signaling has been previously shown to directly control Notch activation in the Drosophila female germline stem cell (GSC) niche, which maintains the niche and GSC identity. Here, we demonstrate that FOXO directly activates transcription of fringe, a gene encoding a glycosyltransferase that modulates Notch glycosylation. Fringe facilitates Notch inactivation in the GSC niche when insulin signaling is low. We also show that the Notch ligand predominantly involved is GSC niche-derived Delta. These results reveal that FOXO-mediated regulation of fringe links the insulin and Notch signaling pathways in the GSC niche in response to nutrition, and emphasize that stem cells are regulated by complex interactions between niche-local and systemic signals.

Keywords: Diet; Glycosylation; Insulin; Notch; Stem cell niche.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Count
  • Cell Nucleus / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / metabolism*
  • Female
  • Forkhead Transcription Factors / metabolism*
  • Germ Cells / cytology*
  • Germ Cells / metabolism*
  • Glycosylation
  • Insulin / metabolism*
  • Models, Biological
  • Molecular Sequence Data
  • Mutation / genetics
  • N-Acetylglucosaminyltransferases / genetics
  • N-Acetylglucosaminyltransferases / metabolism*
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Receptor, Insulin / metabolism
  • Signal Transduction
  • Stem Cell Niche*
  • Transcription, Genetic
  • Zebrafish


  • Drosophila Proteins
  • FOXO protein, Drosophila
  • Forkhead Transcription Factors
  • Insulin
  • N-Acetylglucosaminyltransferases
  • fng protein, Drosophila
  • Receptor, Insulin