A switch in the mode of Wnt signaling orchestrates the formation of germline stem cell differentiation niche in Drosophila

• Published in: PLoS genetics Vol. 14; no. 1; p. e1007154
• Main Authors: Upadhyay, Maitreyi, Kuna, Michael, Tudor, Sara, Martino Cortez, Yesenia, Rangan, Prashanth
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.01.2018; Public Library of Science (PLoS)
• Subjects: Adults; Aging; Biology; Biology and Life Sciences; Cancer; Catenin; Cdc42 protein; Cell adhesion & migration; Cell differentiation; Cell self-renewal; Cell survival; Cellular signal transduction; Drosophila; Females; Gametes; Genetic aspects; Insects; Ligands; Medicine and Health Sciences; Physiological aspects; Rac1 protein; Research and Analysis Methods; RhoA protein; Signal transduction; Stem cells; Transcription; Tumors; Wnt protein; Wnt proteins
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1007154

Germline stem cell (GSC) self-renewal and differentiation into gametes is regulated by both intrinsic factors in the germ line as well as extrinsic factors from the surrounding somatic niche. dWnt4, in the escort cells of the adult somatic niche promotes GSC differentiation using the canonical β-catenin-dependent transcriptional pathway to regulate escort cell survival, adhesion to the germ line and downregulation of self-renewal signaling. Here, we show that in addition to the β-catenin-dependent canonical pathway, dWnt4 also uses downstream components of the Wnt non-canonical pathway to promote escort cell function earlier in development. We find that the downstream non-canonical components, RhoA, Rac1 and cdc42, are expressed at high levels and are active in escort cell precursors of the female larval gonad compared to the adult somatic niche. Consistent with this expression pattern, we find that the non-canonical pathway components function in the larval stages but not in adults to regulate GSC differentiation. In the larval gonad, dWnt4, RhoA, Rac1 and cdc42 are required to promote intermingling of escort cell precursors, a function that then promotes proper escort cell function in the adults. We find that dWnt4 acts by modulating the activity of RhoA, Rac1 and cdc42, but not their protein levels. Together, our results indicate that at different points of development, dWnt4 switches from using the non-canonical pathway components to using a β-catenin-dependent canonical pathway in the escort cells to facilitate the proper differentiation of GSCs.