Wnt Signaling-Mediated Redox Regulation Maintains the Germ Line Stem Cell Differentiation Niche

Elife. 2015 Oct 9;4:e08174. doi: 10.7554/eLife.08174.

Abstract

Adult stem cells continuously undergo self-renewal and generate differentiated cells. In the Drosophila ovary, two separate niches control germ line stem cell (GSC) self-renewal and differentiation processes. Compared to the self-renewing niche, relatively little is known about the maintenance and function of the differentiation niche. In this study, we show that the cellular redox state regulated by Wnt signaling is critical for the maintenance and function of the differentiation niche to promote GSC progeny differentiation. Defective Wnt signaling causes the loss of the differentiation niche and the upregulated BMP signaling in differentiated GSC progeny, thereby disrupting germ cell differentiation. Mechanistically, Wnt signaling controls the expression of multiple glutathione-S-transferase family genes and the cellular redox state. Finally, Wnt2 and Wnt4 function redundantly to maintain active Wnt signaling in the differentiation niche. Therefore, this study has revealed a novel strategy for Wnt signaling in regulating the cellular redox state and maintaining the differentiation niche.

Keywords: D. melanogaster; Gst; Wnt signaling; developmental biology; differentiation niche; germ line stem cells; redox; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Drosophila
  • Drosophila Proteins / metabolism
  • Female
  • Gene Expression Regulation*
  • Germ Cells / physiology*
  • Glutathione Transferase / metabolism
  • Glycoproteins / metabolism
  • Ovary / cytology
  • Oxidation-Reduction
  • Stem Cells / physiology*
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway*
  • Wnt2 Protein / metabolism

Substances

  • Drosophila Proteins
  • Glycoproteins
  • Wnt Proteins
  • Wnt2 Protein
  • Wnt4 protein, Drosophila
  • Glutathione Transferase

Grant support

The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication.