DOI
https://doi.org/10.25772/0NEY-B477
Defense Date
2015
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Integrative Life Sciences
First Advisor
Dr. Gregory S. Walsh
Second Advisor
Dr. Amanda J. Dickinson
Third Advisor
Dr. Michael F. Miles
Fourth Advisor
Dr. Robert M. Tombes
Fifth Advisor
Dr. James A. Lister
Abstract
The Nance-Horan syndrome gene (NHS) plays a role in lens, eye and brain development. To date, the function of NHS remains unclear. Recent evidence showed that p53 isoform, Δ113p53, inhibits abnormal cell growth during organogenesis. We show that NHS is expressed in the retinas of Danio rerio and Xenopus tropicalis during key stages of retinogenesis, and that knockdown of the gene resulted in a small eye phenotype in both species. Initially, knockdown of nhsb in zebrafish had no visible defects at 24hpf. But examination of the retina at 48hpf, we see a marked difference in size compared to control embryos. Cell proliferation is a major feature of the developing retina from 24 hpf to 48 hpf. Differentiation of neurons was delayed, while the total number of cells that makes up the volume of the retina was markedly reduced. Here we show that the small retina in nhsb knockdown embryos are due to p53-dependent cell cycle arrest with specific induction of p53 target gene, Δ113p53 and p21. Δ113p53 protects nhsb- knockdown cells from p53-mediated apoptosis. We hypothesize that nhsb overcomes a proliferation restriction in retina progenitor cells during retinogenesis, while knockdown of nhsb increases expression of Δ113p53 and p21, lengthening the cell cycle.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-22-2015