Ovarian germline stem cell dedifferentiation is cytoneme dependent

• 成果类型: Article
• 署名作者: Sutcliffe, Catherine; Nandy, Nabarun; Revici, Raluca; Johnson, Heather; Habib, Shukry J.; Ashe, Hilary L.; Wilcockson, Scott G.
• 署名单位: University of Manchester; Francis Crick Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10758
• DOI: 10.1073/pnas.2426145122
• 发表日期: 2025-09-02
• 关键词: bag-of-marbles; vasodilator-stimulated phosphoprotein; ena/vasp proteins; morphogen gradient; drosophila fusome; differentiation; transcription; homeostasis; initiation; mechanism

摘要

Progenitor cell dedifferentiation is important for stem cell maintenance during tissue repair and age- related stem cell decline. Here, we use the Drosophila ovary as a model to study the role of cytonemes in bone morphogenic protein (BMP) signaling-directed provide evidence that differentiating germ cell cysts extend longer cytonemes that are more polarized toward the niche during dedifferentiation to reactivate BMP signaling. The presence of additional somatic cells in the niche is associated with a failure of germ cell dedifferentiation, consistent with the formation of a physical barrier to cytoneme- niche contact and outcompetition of germ cells for BMP. Using BMP beads in vitro, tissue culture cells. We demonstrate that the Enabled (Ena) actin polymerase is localized to the tips of germ cell cytonemes and is necessary for robust cytoneme formation, as its mislocalization reduces the frequency, length, and directionality of cytonemes. During impairs GSC fitness by reducing GSC BMP signaling and niche occupancy. Disrupting ness and the ability of differentiating cysts to dedifferentiate. Overall, our results provide evidence that cytonemes play a fundamental role in establishing polarized signaling and niche occupancy during stem cell maintenance and dedifferentiation.