Intestinal stem cell ablation reveals differential requirements for survival in response to chemical challenge

Dev Biol. 2017 Apr 1;424(1):10-17. doi: 10.1016/j.ydbio.2017.01.004. Epub 2017 Jan 17.

Abstract

The Drosophila intestine is maintained by multipotent intestinal stem cells (ISCs). Although increased intestinal stem cell (ISC) proliferation has been correlated with a decrease in longevity, there is some discrepancy regarding whether a decrease or block in proliferation also has negative consequences. Here we identify headcase (hdc) as a novel marker of ISCs and enteroblasts (EBs) and demonstrate that Hdc function is required to prevent ISC/EB loss through apoptosis. Hdc depletion was used as a strategy to ablate ISCs and EBs in order to test the ability of flies to survive without ISC function. While flies lacking ISCs showed no major decrease in survival under unchallenged conditions, flies depleted of ISCs and EBs exhibited decreased survival rates in response to damage to mature enterocytes (EC) that line the intestinal lumen. Our findings indicate that constant renewal of the intestinal epithelium is not absolutely necessary under normal laboratory conditions, but it is important in the context of widespread chemical-induced damage when significant repair is necessary.

Keywords: Drosophila; Headcase; Intestine; Niche; Stem cell.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Biomarkers / metabolism
  • Bleomycin / toxicity
  • Cell Survival / drug effects
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / drug effects
  • Female
  • Intestines / cytology*
  • Regeneration / drug effects
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism

Substances

  • Biomarkers
  • Drosophila Proteins
  • Hdc protein, Drosophila
  • Bleomycin