Co-activator Crosstalk: Yorkie and Taiman interact to regulate niche-to-stem cell signaling in the female Drosophila germline stem cell niche Restricted; Files Only
Wells, Chloe (Spring 2025)
Abstract
Communication between stem cells and the specialized microenvironments they reside in, their “niche,” is vital for organism development and tissue homeostasis. However, pathways that act within a given niche to guide stem cell fates and regulate differentiation of their progeny are not fully understood. The Hippo and Ecdysone nuclear receptor (EcR) signaling pathways have each been shown to regulate stem cell niches in Drosophila tissues, and both are also implicated in human disease. Significantly, these two pathways are linked in the nucleus via a direct, physical interaction between their respective transcriptional coactivators Yorkie (Yki) and Taiman (Tai), and this interaction appears conserved in mammals. Within the female Drosophila germline niche (e.g. the germarium), Yki and Tai have independently been shown to regulate behavior of stem cells and their progeny. It is not known whether the roles of Yki and Tai within the germarium are mechanistically distinct or are regulated by crosstalk between these two co-activators. Here we have utilized a CRISPR mutant fly line containing a form of Tai unable to bind Yki (TaiPPxA) to examine requirements for the Yik-Tai interaction in vivo. A loss of this interaction in TaiPPxA mutants disrupts germline stem cell (GSC) differentiation, stemming from a requirement within escort cells (ECs), a key stomatic niche component. Specifically, the Yki-Tai interaction is required to suppress BMP signaling within ECs and maintain their cellular process, which physically shield differentiating cystoblasts from GSC-targeted signals. In sum, these findings suggest that a Yki-Tai interaction facilitates crosstalk between the Hippo and EcR pathways within ECs, playing a critical role in maintaining intracellular signals that allow escort cells to guide early stages of egg development.
Table of Contents
Chapter 1: Background
Figure 1. Niche interaction model
Figure 2. Drosophila germarium overview
Figure 3. BMP signaling in the germarium
Figure 4. The Hippo pathway is highly conserved
Figure 5. Conservation of Nuclear Receptor Signaling
Figure 6. Inhibiting Yki-Tai interaction reduces female fecundity
Chapter 2: Materials & Methods
Chapter 3: Results
Figure 8. Loss of the Yki-Tai interaction in escort cells causes germline differentiation defects
Figure 9. Loss of the Yki-Tai interaction reduces escort cell processes
Figure 10. Preliminary data shows loss of Yki-Tai interaction causes ectopic BMP pathway activity
Chapter 4: Discussion & Future Directions
Figure 11. Proposed model for the role of Yki-Tai regulation of GSC differentiation
References
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File download under embargo until 22 May 2026 | 2025-04-09 10:56:36 -0400 | File download under embargo until 22 May 2026 |
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