Novel Regulators in the Germline Stem Cell Niche of Drosophila Testis

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Doctor of Philosophy (PhD)
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Drosophila testis
stem cell
stem cell niche
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Stem cells are powerful and promising tools in regenerative medicine. Understanding how stem cells are maintained in vivo is crucial for their clinical application. Studies on various stem cell systems have demonstrated that the stem cell niche, or local tissue microenvironment, provides important extracellular cues to guide stem cell behaviors. The Drosophila male germline system has emerged as an exemplary model for studying stem cell-niche biology. The apically located hub cells function as a shared niche for two stem cell populations: germline stem cells (GSCs) and cyst stem cells (CySCs). A dominant model in the field describes hub cells as the single niche for GSCs via promoting JAK-STAT signaling. However, recent work from our lab has demonstrated that BMP signaling is the primary pathway leading to GSC self-renewal. We have also revealed that CySCs function as a second niche to govern GSC maintenance. In this thesis, we identify Magu as a novel regulator controlling GSC self-renewal. We show that Magu is expressed from hub cells, and specifically required for GSC maintenance. We also show that Magu acts as an extracellular BMP modulator through interaction with Dally-like, a heparan sulfate proteoglycan. Our characterization of Magu further emphasizes the importance of BMP signaling in male GSC maintenance. Zfh1 is a transcription factor expressed in CySCs. Zfh1 is required for CySC maintenance, and can also induce ectopic GSCs non-autonomously. Thus, Zfh1 exerts an impact on two stem cell lineages, matching with our recent notion that CySCs function as both a stem cell and a niche for GSCs. To dissect out how Zfh1 controls stem cell self-renewal, we attempt to identify target genes of Zfh1 using two genome-wide approaches: ChIP-Seq and a genetic modifier screen. Preliminary results show that eya and shg may be direct targets of Zfh1, and CtBP is required for Zfh1 function. This ongoing project will further elucidate the dual role of CySCs, and advance our understanding of the complex niche signals regulating stem cells.

Stephen DiNardo
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