Wnt6 regulates the homeostasis of the stem cell niche via Rac1-and Cdc42-mediated noncanonical Wnt signalling pathways in Drosophila testis

Exp Cell Res. 2021 May 1;402(1):112511. doi: 10.1016/j.yexcr.2021.112511. Epub 2021 Feb 11.

Abstract

The homeostasis of the stem cell niche is regulated by both intrinsic and extrinsic factors, and the complex and ordered molecular and cellular regulatory mechanisms need to be further explored. In Drosophila testis, germline stem cells (GSCs) rely on hub cells for self-renewal and physical attachment. GSCs are also in contact with somatic cyst stem cells (CySCs). Utilizing genetic manipulation in Drosophila, we investigated the role of Wnt6 in vivo and in vitro. In Drosophila testis, we found that Wnt6 is required for GSC differentiation and CySC self-renewal. In Schneider 2 (S2) cells, we found that Wnt6 regulates cell proliferation and apoptosis. Mechanistically, we demonstrated that Wnt6 can downregulate the expression levels of Arm, Rac1 and Cdc42 in S2 cells. Notably, Rac1 and Cdc42, which act downstream of the noncanonical Wnt signalling pathway, imitated the phenotypes of Wnt6 in Drosophila testis. Thus, the newly discovered Wnt6-Rac1/Cdc42 signal axis is required for the homeostasis of the stem cell niche in the Drosophila testis.

Keywords: Cdc42; Drosophila; Rac1; Stem cell niche; Wnt signalling; Wnt6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Differentiation / genetics
  • Cell Proliferation / genetics
  • Drosophila Proteins / genetics*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • GTP-Binding Proteins / genetics*
  • Gene Expression Regulation, Developmental / genetics
  • Germ Cells / metabolism
  • Homeostasis / genetics
  • Male
  • Stem Cell Niche / genetics
  • Stem Cells / metabolism
  • Testis / growth & development*
  • Testis / metabolism
  • Wnt Proteins / genetics*
  • rac GTP-Binding Proteins / genetics*

Substances

  • Cdc42 protein, Drosophila
  • Drosophila Proteins
  • Rac1 protein, Drosophila
  • Wnt Proteins
  • Wnt6 protein, Drosophila
  • GTP-Binding Proteins
  • rac GTP-Binding Proteins