Adult stem cells reside in specialized microenvironments called niches, which provide signals for stem cells to maintain their undifferentiated and self-renewing state. To maintain stem cell quality, several types of stem cells are known to be regularly replaced by progenitor cells through niche competition. However, the cellular and molecular bases for stem cell competition for niche occupancy are largely unknown. Here, we show that two Drosophila members of the glypican family of heparan sulfate proteoglycans (HSPGs), Dally and Dally-like (Dlp), differentially regulate follicle stem cell (FSC) maintenance and competitiveness for niche occupancy. Lineage analyses of glypican mutant FSC clones showed that dally is essential for normal FSC maintenance. In contrast, dlp is a hypercom-petitive mutation: dlp mutant FSC progenitors often eventually occupy the entire epithelial sheet. RNA interference knockdown experiments showed that Dally and Dlp play both partially redundant and distinct roles in regulating Jak/Stat, Wg, and Hh signaling in FSCs. The Drosophila FSC system offers a powerful genetic model to study the mechanisms by which HSPGs exert specific functions in stem cell replacement and competition.
Bibliographical noteFunding Information:
We are grateful to T. Nystul, R. DasGupta, J. P. Vincent, H. Jiang, B. Dickson, the Developmental Studies Hybridoma Bank, the Bloomington Stock Center, Kyoto Stock Center, Vienna Drosophila Resource Center, and the Drosophila Transgenic RNAi Project at Harvard Medical School for fly stocks and reagents. We thank A. Toth, M. Takemura and D. Levings for helpful discussions and critical reading of the manuscript. This work was partly supported by the National Institutes of Health (grant R01 GM115099 to H.N).
© 2018, Genetics Society of America. All rights reserved.
- Follicle stem cells
- Heparan sulfate
- Stem cell competition