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

Abstract

To remain self-renewal or to differentiate, this is one of the most important question in the stem cell field. Both stem cell maintenance and differentiation are regulated by intrinsic and extrinsic signals from surrounding stromal cells or niche. The Drosophila ovary is a simple but elegant model to study stem cells and their niche. At the tip of Drosophila ovary, a cluster of somatic cap cells form the germline stem cell niche and provide self-renewal signal to maintain GSC self-renewal. When GSC divides, its daughter cell, cystoblast leaves the GSC niche and undergoes differentiation. Outside the self-renewal niche, inner sheath cells are required for germ cell differentiation by functioning as a germ cell differentiation niche. Compared to the self-renewing niche, relatively little is known about the maintenance and function of the differentiation niche. Here we show that the cellular redox state regulated by Wnt signaling is critical for the maintenance and function of the differentiation niche to promote germ cell differentiation. Defective Wnt signaling results in the loss of the differentiation niche, and thus a germ cell differentiation defect. 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.