Date of Award

Spring 2009

Document Type

Restricted Thesis

Terms of Use

© 2009 Mark Mai. All rights reserved. Access to this work is restricted to users within the Swarthmore College network and may only be used for non-commercial, educational, and research purposes. Sharing with users outside of the Swarthmore College network is expressly prohibited. For all other uses, including reproduction and distribution, please contact the copyright holder.

Degree Name

Bachelor of Arts

Department

Biology Department

First Advisor

Scott F. Gilbert

Abstract

The nephron, the basic functional unit of the kidney, is composed of a glomerulus (blood filter) and a tubular epithelium. The complexity of the mammalian metanephric kidney has hindered research on the developmental genetics driving the segmentation of nephrons. In the past decade, the zebrafish pronephros has emerged as a genetic model for nephric segmentation because of its ability to combine simplicity with a pattern of gene expression that is shared with the developing mammalian kidney. In this thesis, I confirm a conserved role for pax2.1 and pax8 in the genetic regulation of zebrafish pronephric segmentation; the involvement of these genes in renal development has been previously reported in mice. In addition to truncating the distal tubule segments, pax2.1 and pax8 knockdowns cause lengthening of proximal segments, a previously unreported phenotype. To identify novel genes involved in the segmentation of the nephron, I gathered preliminary data from an ongoing forward genetic screen. Using in situ hybridization, I identified six families of fish with abnormal podocytes, which are specialized cells that comprise the blood filtration barrier in the glomerulus. Two mutants were further characterized using podocyte markers that appear at different stages of development. Using these criteria, the mutants can be classified into groups that have: (1) reduced number of podocytes, (2) podocytes that failed to migrate and fuse, and (3) podocytes that exhibit developmental delay/arrest. This thesis provides further evidence that the zebrafish pronephros is a powerful genetic model for mammalian nephric segmentation and identifies new classes of podocyte mutants.

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