Diet controls normal and tumorous germline stem cells via insulin-dependent and -independent mechanisms in Drosophila

Hwei Jan Hsu, Leesa LaFever, Daniela Drummond-Barbosa

Research output: Contribution to journalArticlepeer-review

Abstract

The external environment influences stem cells, but this process is poorly understood. Our previous work showed that germline stem cells (GSCs) respond to diet via neural insulin-like peptides (DILPs) that act directly on the germ line to upregulate stem cell division and cyst growth under a protein-rich diet in Drosophila. Here, we report that DILPs specifically control the G2 phase of the GSC cell cycle via phosphoinositide-3 kinase (PI3K) and dFOXO, and that a separate diet mediator regulates the G1 phase. Furthermore, GSC tumors, which escape the normal stem cell regulatory microenvironment, or niche, still respond to diet via both mechanisms, indicating that niche signals are not required for GSCs to sense or respond to diet. Our results document the effects of diet and insulin-like signals on the cell cycle of stem cells within an intact organism and demonstrate that the response to diet requires multiple signals. Moreover, the retained ability of GSC tumors to respond to diet parallels the long known connections between diet, insulin signaling, and cancer risk in humans.

Original languageEnglish (US)
Pages (from-to)700-712
Number of pages13
JournalDevelopmental biology
Volume313
Issue number2
DOIs
StatePublished - Jan 15 2008
Externally publishedYes

Keywords

  • Cell cycle
  • Clonal analysis
  • Diet
  • Drosophila
  • Germline stem cell
  • Insulin pathway
  • Oogenesis
  • Proliferation
  • Tumor

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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