Analysis of Renal Development: Genetic Mechanisms of Distal Nephron Cell Fate Specification Involving Emx Genes

Doctoral Dissertation
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Abstract

The human body is a complex biological machine composed of various parts. Each part or organ within the organism has a specific function that serves to efficiently keep the body alive and when these organ functions are hampered, either through injury or through a developmental defect in the organ, the organism’s health is placed at risk. Your kidneys are an intricate biological system compose of two bean-shaped organs, approximately the size of your clenched fist, that is mainly responsible for blood filtration, waste metabolite removal, and homeostasis maintenance. They are made up of small, functional nephrons units characterized by the presence of a blood-filtering glomerulus connected to an epithelial tubule made up of distinct proximal and distal segments, each one responsible for various important tasks such as nutrient reabsorption or pH regulation. Due to our body’s limited regenerative capacity, anything that disturbs this intricate blood filtering array composed of nephrons can potentially lead to kidney conditions that severely hamper your body’s ability to filter blood. In fact, chronic kidney disease is the 9th leading cause of the death in the U.S., and current treatments only serve as a stop-gap measure, as they cannot ameliorate damage, only manage symptoms. Our overarching goal is to further our understanding of renal ontogeny by elucidating the molecular and genetic mechanisms of nephron tubule segment formation. Here we use the zebrafish, a versatile animal model, to study kidney development, develop new tissue manipulation techniques for researcher to study localized signaling molecule function, and reveal novel roles for the conserved emx1 and emx2 transcription factors in during nephrogenesis. In general, we observed that emx1 controls distal segment cell fate by promoting the distal late segment while inhibiting formation of the distal early. Additionally, preliminary studies on emx2 function reveal that the transcription factor may have a role in controlling formation of the proximal straight tubule. Understanding how nephrons are formed will lead to further insights into kidney disease onset and progression, which will ultimately lead to the development of better therapies for kidney disease patients.

Attributes

Attribute NameValues
Author Elvin E. Morales
Contributor Athanasia Panopoulos, Committee Member
Contributor Molly Duman Scheel, Committee Member
Contributor Rebecca A. Wingert, Research Director
Contributor Joseph E O'Tousa, Committee Member
Degree Level Doctoral Dissertation
Degree Discipline Biological Sciences
Degree Name Doctor of Philosophy
Banner Code
  • PHD-BIOS

Defense Date
  • 2018-11-16

Submission Date 2019-04-08
Record Visibility and Access Public
Content License
  • All rights reserved

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