The Role of the RNA-Induced Silencing Complex (RISC) Component VIG-1 in Caenorhabditis elegans Germline Stem Cell Regulation
Date
2021-04-26
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Abstract
Stem cells are undifferentiated cells that can give rise to a wide variety of specialized cell types. In development and tissue maintenance, these cells play crucial roles in maintaining homeostasis and reproductive fitness. The C. elegans germline is a powerful model in which the nature of stem cell regulation can be studied. The germline is set up in an assembly line-like format, in which mitotically dividing proliferative cells reside in a distal niche. As cells move away from this niche, they gradually undergo meiosis until becoming fully differentiated sperm or oocytes. Notch signaling in the distal end of the germline provides the proliferative signal, while downstream post-transcriptional regulatory pathways promote differentiation. Although this main pathway has been well characterized, various components serve to fine-tune this balance in subtle but important ways. Previous work has identified small RNA molecules, such as miRNAs, as having a role in germline stem cell regulation. In this thesis, the role of vig-1, a gene involved in the RNA-induced silencing complex (RISC) pathway, in C. elegans germline stem cell regulation is investigated. Although vig-1 performs multiple functions in a variety of tissues, it was initially implicated in the germline through its physical protein interaction with another RISC pathway component, teg-1, that was known to modulate germline stem cell balance. Here, I show that vig-1 functions to repress the activity of Notch signaling. In worms lacking vig-1 activity, Notch signaling is seen to be enhanced, manifesting through ectopic over-proliferation of stem cells. Furthermore, vig-1 can partially suppress Notch loss-of-function mutant phenotypes. Using immunofluorescent microscopy, I show that vig-1 may act directly on Notch signaling through increasing the expression of its direct transcriptional targets. I also show that vig-1 does not work with downstream differentiation-promoting pathways, further strengthening the idea that vig-1 functions at the level of Notch signaling. Finally, I propose a potential miRNA mechanism through which vig-1 exerts its function on the germline proliferation versus differentiation decision. This work provides deeper insight into the complex and interwoven nature of regulatory signaling pathways and lays the foundation for further research and eventual therapeutic or biotechnological applications.
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C. elegans, Developmental Biology, Stem Cells, Genetics
Citation
Zhang, D. J. R. (2021). The Role of the RNA-Induced Silencing Complex (RISC) Component VIG-1 in Caenorhabditis elegans Germline Stem Cell Regulation (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.