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

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 (Tai^PPxA) to examine requirements for the Yik-Tai interaction in vivo. A loss of this interaction in Tai^PPxA 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

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Cell Biology, Genetics
Parola chiave	Nuclear receptor signaling Drosophila melanogaster Stem cell niche Hippo pathway
Committee Chair / Thesis Advisor	Ken Moberg, Emory University
Committee Members	Leila Rieder, Emory University Dave Gorkin, Emory University

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