Mechanisms Regulating Photoreceptor Subtype Specification and Chromophore Utilization in Zebrafish
Date of Award
Doctor of Philosophy (PhD)
The first step in vision is the detection of light by a photoreceptor cell. The spectral sensitivity of a photoreceptor, in turn, is determined by the composition of its visual pigment, which consists of an opsin protein and a covalently bound chromophore derived from either vitamin A1 or vitamin A2. In the course of evolution, opsin gene duplication and functional divergence led to the emergence of four distinctive cone opsins, maximally sensitive to ultraviolet (UV), blue, green, or red light, as well as the rod opsin. Subsequently, the expression of these functionally distinct opsins was segregated into distinct cell types via the action of transcriptional regulatory networks. The zebrafish (Danio rerio) retina contains four cone subtypes and one rod. In addition, zebrafish utilize the P450 enzyme, Cyp27c1, to convert vitamin A1- into A2-based chromophores—to red-shift the spectral sensitivity of the visual pigments. The objective of this thesis is to understand the transcriptional networks that govern photoreceptor subtype diversification and chromophore selection in zebrafish.
In my studies, I identified novel transcriptional mechanisms that regulate photoreceptor subtype specification, opsin expression, and chromophore utilization. I first analyzed the role of thyroid hormone (TH) receptor transcription factors (TFs) in regulating cyp27c1. I found that no single TH receptor is required for cyp27c1 expression but that elimination of all three TH receptors completely abrogates cyp27c1 expression and vitamin A2 production in zebrafish. Next, I studied the role of thrb in red cones. I found that thrb mutant red cones fail to develop and are instead transfated into UV cones and possibly horizontal cells. Lastly, I determined the role of the transcriptional corepressor, samd7 in zebrafish photoreceptor development. I observed a loss of rods, a transfating of green cones to blue cones, and the transformation of red cones into a hybrid photoreceptor type co-expressing both red and UV opsins in samd7 mutant zebrafish. Thus, Samd7 plays a critical role in repressing short-wavelength cone (i.e., blue and UV) gene expression in long-wavelength cones (i.e., green and red). Taken together, my studies expand our knowledge of the transcriptional mechanisms that regulate photoreceptor subtype diversification and chromophore utilization in zebrafish.
Chair and Committee
Joseph C. Corbo
Shiming Chen, Harrison W. Gabel, Vladimir J. Kefalov, Jame B. Skeath
Volkov, Leo, "Mechanisms Regulating Photoreceptor Subtype Specification and Chromophore Utilization in Zebrafish" (2022). Arts & Sciences Electronic Theses and Dissertations. 2815.
Available for download on Saturday, December 21, 2024