Examining the Roles of the Receptor Tyrosine Kinase PVR and the Bone Morphogenic Protein Receptor Thickvein in Regulating Self-Renewal and Division Frequency in the Cyst Stem Cells of the Drosophila Testis Niche
University of Northern Colorado
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University of Northern Colorado
Adult stem cells live in different tissues, and they support and regenerate both the tissue they reside in and themselves. The stemness behavior is tightly regulated by the niche. The Drosophila testis is a valuable model to study stem cells in their niche. In this niche, there are two populations of stem cells; germline stem cells (GSCs) and somatic cyst stem cells (CySCs). GSCs and CySCs provide the cellular structure required to maintain the production of sperm in Drosophila males. These stem cells co-mingle around a group of non-dividing somatic cells known as the hub, and is the niche that provides molecular signals to instruct the behavior of stem cells. The fate of GSCs and differentiating germ cells is dependent on CySCs and their descendants, cyst cells, because if these cells are blocked, GSCs would be unable to be maintained normally as stem cells or differentiate properly. This dissertation describes the role of PVR and BMP signaling pathways in the CySCs of the Drosophila testis stem cell niche. PVR signaling regulates the cell division frequency of the CySCs in the stem cell niche. This was shown by loss of function experiments, as inhibiting PVR in the CySCs by RNA interference and dominant negative transgene expression resulted in significant reduction of CySCs at the niche and the cycling CySCs and disruption of transit amplifying germ cells non-autonomously. It was also demonstrated by constitutive PVR expression, or ectopic Pvf1 ligand expression, which resulted in tumorous accumulation of cyst lineage cells throughout the testis, and misregulated cycling of these cells outside of the niche. PVR might also play a role in stem cell competition at the niche. PVR mutant CySCs clones do not persist as stem cells in the testis and PVR mutant clones are out competed with the wildtype CySCs. Our result also demonstrated that when constitutively activate PVR is combined with tumor suppressor Merlin over-expression in the cyst cells lineage, Merlin suppresses PVR signaling and is able to prevent any tumor formation due to hyperproliferation of cyst cells in the testis. BMP signaling pathway is the main self-renewal regulator in GSCs. We have examined the requirement for BMP signaling in the CySCs and demonstrated that BMP signaling pathway regulates stem cell maintenance in the Drosophila testis stem cell niche. When we ablated tkv, the type I receptor of BMP pathway in the cyst lineage cells by RNA interference, we observed a partial loss of CySCs and loss of differentiated cyst cells. In the absence of cyst cells, the germline cells were also incapable of completing differentiation and the number of GSCs also decreased in the manipulated testes showing the non-autonomous effect of ablating BMP pathway in CySCs on the population of GSCs.
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