The Derlin protein CUP-2’s role in regulating the Caenorhabditis elegans germline stem cell niche, the Distal Tip Cell
Date
2021-08-19
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Abstract
The balance between stem cell proliferation and differentiation is important for growth and development in various multicellular organisms. This balance is highly regulated, and it requires an interaction between the niche and the stem cell pool in order to be upheld. The presence of a stem cell niche is highly conserved; however, depending on the organism and system they can act through a variety of signaling pathways to maintain the stem cell pool. In C. elegans, the somatic distal tip cell (DTC) acts as the germline stem cell niche by providing cues via GLP-1/Notch signalling. We have identified that the Derlin protein DER-1 (CUP-2) plays a role in regulating the DTC. Normally, the DTC is located at the distal end of the gonad. As worms age, it can move several cell diameters away from the distal most end (Kocsisova et al., 2019). However, as cup-2 mutant worms age, the DTC moves significantly further down the gonad arm than what is seen with wild type. In some more extreme and rare cases where the DTC has moved at least 10 cells from the distal end, the stem cell pool moves along with the DTC. The stem cells are still able to proliferate and differentiate at this new location, which suggests the DTC remains functional at the new location. In this thesis, cup-2’s role in holding the DTC in place has been investigated. First, the displacement and two transition zone phenotypes have been characterized further. Additionally, male strains were investigated to determine whether or not the DTC displacement phenotype is sexually dimorphic. Next, I determined where cup-2 is expressed and required such that the DTC will remain in place. Also, I explored cup-2’s known functions, endoplasmic reticulum associated degradation (ERAD) and endocytosis, to determine if they play a role in the placement of the DTC. Finally, I investigated components involved in the surrounding basement membrane to determine if cup-2 may play a novel role in regulating the basement membrane. This investigation of CUP-2 and the DTC may help us understand how the DTC and potentially other niches are held in place.
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Keywords
C. elegans, CUP-2, Derlin, ERAD, Basement membrane, Stem cell niche
Citation
McMillan, L. (2021). The Derlin protein CUP-2’s role in regulating the Caenorhabditis elegans germline stem cell niche, the Distal Tip Cell (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.