YAP/Yorkie in the germline modulates the age-related decline of germline stem cells and niche cells

PLoS One. 2019 Apr 3;14(4):e0213327. doi: 10.1371/journal.pone.0213327. eCollection 2019.

Abstract

The properties and behaviour of stem cells rely heavily on signaling from the local microenvironment. At the apical end of Drosophila testis, self-renewal and differentiation of germline stem cells (GSCs) are tightly controlled by distinct somatic cells that comprise a specialised stem cell niche known as the hub. The hub maintains GSC homeostasis through adhesion and cell signaling. The Salvador/Warts/Hippo (SWH) pathway, which suppresses the transcriptional co-activator YAP/Yki via a kinase cascade, is a known regulator of stem cell proliferation and differentiation. Here, we show that increasing YAP/Yki expression in the germline, as well as reducing Warts levels, blocks the decrease of GSC numbers observed in aging flies, with only a small increase on their proliferation. An increased expression of YAP/Yki in the germline or a reduction in Warts levels also stymies an age-related reduction in hub cell number, suggesting a bilateral relationship between GSCs and the hub. Conversely, RNAi-based knockdown of YAP/Yki in the germline leads to a significant drop in hub cell number, further suggesting the existence of such a SC-to-niche relationship. All together, our data implicate the SWH pathway in Drosophila GSC maintenance and raise questions about its role in stem cell homeostasis in aging organisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Germline Stem Cells / physiology*
  • Aging / physiology*
  • Animals
  • Animals, Genetically Modified
  • Cell Cycle Proteins / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Female
  • Fertility / physiology
  • Gene Knockdown Techniques
  • Male
  • Models, Animal
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Kinases / metabolism
  • RNA Interference
  • Signal Transduction / physiology
  • Stem Cell Niche / physiology*
  • Testis / cytology
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • YAP-Signaling Proteins

Substances

  • Cell Cycle Proteins
  • Drosophila Proteins
  • Nuclear Proteins
  • Trans-Activators
  • YAP-Signaling Proteins
  • Yki protein, Drosophila
  • sav protein, Drosophila
  • Protein Kinases
  • wts protein, Drosophila