Date of Graduation
12-2020
Document Type
Dissertation (PhD)
Program Affiliation
Genes and Development
Degree Name
Doctor of Philosophy (PhD)
Advisor/Committee Chair
Rachel K. Miller, Ph.D.
Committee Member
Richard Behringer, Ph.D.
Committee Member
Andrew B. Gladden, Ph.D.
Committee Member
Yoshihiro Komatsu, Ph.D.
Committee Member
Pierre D. McCrea, Ph.D.
Committee Member
Oleh M. Pochynyuk, Ph.D.
Abstract
Kidneys, like most organs in our bodies, consist of a network of epithelial tubules. Kidney tubules are called nephrons, and their morphology is important for kidney function. Nephrons develop from mesodermally derived aggregates of progenitor cells. The nephric progenitors organize into nephric tubules lined with hair-like sensory projections called cilia. Many diseases of the kidney are characterized by abnormal nephron morphology with current treatment aimed at symptom control. To understand the mechanisms underlying kidney diseases and achieve the development of novel therapies, a better understanding of how nephrons develop is needed. Although the actin cytoskeleton is critical for cell behaviors underlying nephron morphogenesis, we still know very little about the regulation of cytoskeletal dynamics. Here, we examine the role of the Wnt/Planar Cell Polarity formin, Dishevelled-associated activator of morphogenesis 1 (Daam1), in shaping nephric tubules. We show that Daam1 governs nephron morphology by regulating E-cadherin-based cell-cell adhesion of progenitor cells and junctional actin filaments' stability. We also report divergent roles for Daam1 in ciliogenesis. This dissertation enhances our understanding of cytoskeletal regulation, adhesion, and organizational behaviors involved in nephron assembly.
Keywords
Kidney, Nephron, actin, E-cadherin, Daam1, Wnt, Formin, cell adhesion
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