Author ORCID Identifier

https://orcid.org/0000-0002-0898-8741

Date of Graduation

8-2022

Document Type

Thesis (MS)

Program Affiliation

Biomedical Sciences

Degree Name

Masters of Science (MS)

Advisor/Committee Chair

Rachel K Miller, Ph.D

Committee Member

Pierre McCrea, Ph.D

Committee Member

George Eisenhoffer, Ph.D

Committee Member

Yoshihiro Komatsu, Ph.D

Committee Member

Ruth Heidelberger, MD, Ph.D

Abstract

Congenital anomalies of the kidney and urinary tract (CAKUT) accounts for nearly one-fourth of all birth defects and more than 40% of pediatric end-stage renal disease, yet only 10-20% of CAKUT cases have a known monogenetic cause. Human kidneys are composed of up to a million epithelial tubules called nephrons. Disruption of nephron development is one of the many congenital anomalies that cause CAKUT, often resulting in chronic or end-stage renal disease which requires transplant. During nephron epithelialization, the formation of stable cadherin-mediated adhesion junctions is essential for maintaining cell-cell contacts. To understand the cell behaviors underlying abnormalities in renal morphology and cyst formation and to facilitate the application of novel treatments for congenital birth defects, a better understanding of the cellular mechanisms driving cell junction formation during nephron formation is needed. Given that adhesion complex components are known to be transported via membrane vesicles, we examine the role of the exocyst-associated scaffolding protein, Dynamin binding protein (Dnmbp), during junction assembly in epithelializing nephric tubules. We show that disruption of Dnmbp affects adhesion and junctional integrity of nephron progenitor cells by significantly reducing junctional E-cadherin localization when compared with standard controls. Additionally, Dnmbp-depleted nephron progenitor cells appear to have disordered membrane borders, further indicating a reduction in junctional integrity. This thesis enhances our understanding of adhesion and junctional integrity of nephron progenitor cells during epithelialization.

Keywords

Organogenesis, Nephrogenesis, Epithelialization, Adherens Junctions, Vesicle Transport

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