Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Date of Award

Spring 2018

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Department of Biology

Advisor(s)

Raymond A. Enke

Steven G. Cresawn

Kimberly H. Slekar

Abstract

The retina, the sensory neuronal tissue within the eye, is composed of three layers of neuronal cells connected by two synaptic layers lining the inside of the anterior portion of the eye. Multipotent retinal precursor cells are genetically homogeneous and differentiate into mature retinal neurons due to differential gene expression. Differences in gene expression have been correlated with epigenetic modifications such as DNA methylation. DNA methylation of upstream regulatory elements is associated with transcriptional silencing of gene expression. Years of research in retinal development has identified the numerous genes expressed during the main steps of retinal development, however, it is unclear how epigenetic modifications such as DNA methylation influence the expression of the genes. Several studies have correlated methylation patterns with expression levels of specific genes such as Rhodopsin (RHO) and Retinal Binding Protein 3 (RBP3), however, there is a lack of knowledge regarding the changes in methylation and gene expression patterns during retinal development of many other photoreceptor genes. In an attempt to characterize the role of DNA methylation in regulating developmental-specific patterns of gene expression in the retina, this project correlates chicken (Gallus gallus) whole-genome bisulfite sequencing (WGBS) data with RNA-seq data to identify a novel set of epigenetically-regulated genes involved in retinal development. Further gene specific analyses indicate an inverse relationship between methylation and expression in several retinal genes (PRPH2, FSCN2, LRIT1) while other genes (ARR3, PDE6B, PDE6C, GNAT1) do not show the same relationship. Additional analysis of the DMRs accompanying the DEGs can answer questions about the mechanisms by which DNA methylation is influencing gene expression. By correlating the differentially expressed genes with the differentially methylated regions of the developing retina, we can begin to understand the role of DNA methylation in producing functional retinal cells from retinal pluripotent cells. This knowledge can give insights into how to generate retinal neurons to better treat retinal degenerative diseases.

Available for download on Thursday, April 23, 2020

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