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You searched for +publisher:"McMaster University" +contributor:("Bridgewater, Darren"). Showing records 1 – 2 of 2 total matches.

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McMaster University

1. KITALA, PATRICIA. Characterization of the Role of Shroom3 in Nephron Formation.

Degree: MSMS, 2019, McMaster University

Proper development of the nephron, the functional unit of the kidney, is essential for kidney function. The nephron develops from a pool of cap mesenchymal cells, as defined by a cluster of cells adjacent to the ureteric bud tips of branching ureteric epithelium, giving rise to two subset populations: the self renewing cells and the nephron progenitors. These nephron progenitors undergo mesenchymal-epithelial transition (MET) to develop into polarized renal vesicles (RV), and eventually fuse with the epithelial tubule to develop into a mature nephron. Although these processes are essential for the formation of functional kidneys, little is known about the molecular mechanisms that regulate them. In this study, we characterize several steps during cap mesenchyme and renal vesicle formation using our Shroom3 knockout mouse kidney as our model. Previous researchers have associated Shroom3 with chronic kidney disease. Detecting and analyzing the genetic components of CKD is needed to improve our understanding of its pathogenesis. Shroom3 encodes an actin-binding protein that regulates cell shape changes through induction of apical constriction. However, there is a lack of evidence about Shroom3’s expression pattern and functional role upstream of developed nephrons. Here, I defined the spatial and temporal expression of Shroom3 within the cap mesenchyme region. I investigated the nephron progenitors between Shroom3 wildtypes and mutants. Lastly, I analyzed the renal vesicle polarity in mutants, by analyzing apical membrane markers on RVs to characterize any abnormalities in their orientation and establishment of polarity.

Thesis

Master of Science in Medical Sciences (MSMS)

Advisors/Committee Members: BRIDGEWATER, DARREN.

Subjects/Keywords: Shroom3; Kidney

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

KITALA, P. (2019). Characterization of the Role of Shroom3 in Nephron Formation. (Masters Thesis). McMaster University. Retrieved from http://hdl.handle.net/11375/24826

Chicago Manual of Style (16th Edition):

KITALA, PATRICIA. “Characterization of the Role of Shroom3 in Nephron Formation.” 2019. Masters Thesis, McMaster University. Accessed February 27, 2021. http://hdl.handle.net/11375/24826.

MLA Handbook (7th Edition):

KITALA, PATRICIA. “Characterization of the Role of Shroom3 in Nephron Formation.” 2019. Web. 27 Feb 2021.

Vancouver:

KITALA P. Characterization of the Role of Shroom3 in Nephron Formation. [Internet] [Masters thesis]. McMaster University; 2019. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/11375/24826.

Council of Science Editors:

KITALA P. Characterization of the Role of Shroom3 in Nephron Formation. [Masters Thesis]. McMaster University; 2019. Available from: http://hdl.handle.net/11375/24826


McMaster University

2. Cunanan, Joanna. Quercetin Inhibits β-catenin Transcriptional Activity During Kidney Development and Reduces the Severity of Renal Dysplasia.

Degree: MSMS, 2019, McMaster University

M.Sc. Thesis Dissertation, August 2019, McMaster University

Renal dysplasia, defined as the abnormal development of kidney tissue, is the leading cause of kidney disease in children. While there are numerous causes of renal dysplasia (i.e. genetic, environmental and epigenetic factors), there is no cure to this abnormal defect. Kidney development occurs by two main processes: branching morphogenesis, which forms the collecting duct system, and nephrogenesis, which generates the nephrons, the functional units of the kidney. Our previous studies have demonstrated that β-catenin, a dual-function protein involved in cell adhesion and gene transcription, regulates branching morphogenesis and nephrogenesis. Furthermore, we discovered that nuclear β-catenin levels are increased in kidneys from patients with renal dysplasia, suggesting β-catenin can be a potential therapeutic target to modulate kidney development and renal dysplasia. Quercetin is a flavonoid that reduces β-catenin levels and inhibits its transcriptional activity, leading to improved outcomes in cancer and in kidney fibrosis. The role of quercetin in kidney development and in abnormal defects that arise during kidney development is yet to be examined. Using embryonic mouse kidney organ culture, I found that quercetin treatment resulted in a dose-dependent disruption in branching morphogenesis and nephrogenesis. In addition, quantitative reverse-transcriptase PCR revealed a decreased expression of β-catenin target genes essential for kidney development (i.e. Pax2, Six2 and GDNF). Immunohistochemistry for β-catenin demonstrated that quercetin reduced nuclear β-catenin expression and increased cytoplasmic and membrane-bound expression in a dose-dependent manner. These results were confirmed by Western blot analysis. These novel findings demonstrate that quercetin treatment resulted in decreased levels of nuclear β-catenin, resulting in a decrease in its transcriptional activity which manifested in alterations in kidney developmental processes, suggesting quercetin is effective at reducing nuclear β-catenin in wild-type embryonic kidneys. Next, to determine whether quercetin has any effects on renal dysplasia, I utilized transgenic mice models that overexpress β-catenin in select cells of the embryonic kidney. These models recapitulate the defects observed in human renal dysplasia, including disorganized branching morphogenesis and disrupted nephrogenesis. Quercetin treatment of embryonic dysplastic kidneys resulted in a partial rescue of renal dysplasia which was evident in marked improvements in branching morphogenesis and nephrogenesis, as well as an increase in the number of properly-developing nephrons in the kidney tissue. Analysis of β-catenin expression in quercetin-treated dysplastic kidneys revealed a decrease in nuclear levels and an increase in cytoplasmic and membrane-bound levels, resulting in a reduced expression of target genes (Pax2, Six2, and GDNF). Finally, this partial rescue of renal dysplasia was associated with an improved and organized…

Advisors/Committee Members: Bridgewater, Darren, Medical Sciences (Growth and Development).

Subjects/Keywords: kidney development; beta-catenin; renal dysplasia; quercetin

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Cunanan, J. (2019). Quercetin Inhibits β-catenin Transcriptional Activity During Kidney Development and Reduces the Severity of Renal Dysplasia. (Masters Thesis). McMaster University. Retrieved from http://hdl.handle.net/11375/24793

Chicago Manual of Style (16th Edition):

Cunanan, Joanna. “Quercetin Inhibits β-catenin Transcriptional Activity During Kidney Development and Reduces the Severity of Renal Dysplasia.” 2019. Masters Thesis, McMaster University. Accessed February 27, 2021. http://hdl.handle.net/11375/24793.

MLA Handbook (7th Edition):

Cunanan, Joanna. “Quercetin Inhibits β-catenin Transcriptional Activity During Kidney Development and Reduces the Severity of Renal Dysplasia.” 2019. Web. 27 Feb 2021.

Vancouver:

Cunanan J. Quercetin Inhibits β-catenin Transcriptional Activity During Kidney Development and Reduces the Severity of Renal Dysplasia. [Internet] [Masters thesis]. McMaster University; 2019. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/11375/24793.

Council of Science Editors:

Cunanan J. Quercetin Inhibits β-catenin Transcriptional Activity During Kidney Development and Reduces the Severity of Renal Dysplasia. [Masters Thesis]. McMaster University; 2019. Available from: http://hdl.handle.net/11375/24793

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