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

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.