mastermind regulates niche ageing independently of the Notch pathway in the Drosophila ovary

Open Biol. 2019 Nov 29;9(11):190127. doi: 10.1098/rsob.190127. Epub 2019 Nov 20.

Abstract

Proper stem cell activity in tissues ensures the correct balance between proliferation and differentiation, thus allowing tissue homeostasis and repair. The Drosophila ovary develops well-defined niches that contain on average 2-4 germline stem cells (GSCs), whose maintenance depends on systemic signals and local factors. A known player in the decline of tissue homeostasis is ageing, which correlates with the waning of resident stem cell populations. In Drosophila, ovaries from old females contain fewer GSCs than those from young flies. We isolated niche cells of aged ovaries, performed a transcriptomic analysis and identified mastermind (mam) as a factor for Drosophila ovarian niche functionality during ageing. We show that mam is upregulated in aged niche cells and that we can induce premature GSC loss by overexpressing mam in otherwise young niche cells. High mam levels in niche cells induce reduced Hedgehog amounts, a decrease in cadherin levels and a likely increase in reactive oxygen species, three scenarios known to provoke GSC loss. Mam is a canonical co-activator of the Notch pathway in many Drosophila tissues. However, we present evidence to support a Notch-independent role for mam in the ovarian germline niche.

Keywords: DE-cadherin; Drosophila oogenesis; Hedgehog; mastermind; niche ageing; reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Cellular Senescence
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / physiology*
  • Female
  • Germ Cells / cytology
  • Germ Cells / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Ovary / cytology
  • Ovary / physiology
  • Receptors, Notch / metabolism*
  • Signal Transduction*
  • Stem Cell Niche
  • Transcriptome

Substances

  • Drosophila Proteins
  • N protein, Drosophila
  • Nuclear Proteins
  • Receptors, Notch
  • mam protein, Drosophila