Idris Korol
Major: Biology
Faculty Advisor: Deborah Stenkamp, Ph.D.
Project Title:
Predicted Palindromic Thyroid Hormone Response Elements Affect the Thyroid Hormone Regulation of Opsin Expression in Zebrafish
Abstract
Cone opsins are light-sensitive proteins expressed by cone photoreceptors of the vertebrate retina that mediate high-acuity color vision. In humans, the long wavelength-sensitive (LWS) and medium wavelength- sensitive (MWS) opsins emerged from a tandem duplication event. Similarly, zebrafish have a lws1/lws2 gene array that arose from an independent tandem duplication event and shares a common ancestral gene with the human LWS/MWS genes.
Our lab has previously found that thyroid hormone (TH) regulates the zebrafish gene array, and this study aims to understand how the TH regulation of lws1/lws2 occurs. Previous research has shown that the 0.6kb region upstream of lws1 likely plays a role in the TH regulation of the lws locus. Genomic prediction tools identified two stretches of sequences as possible TH receptor binding regions – these are referred to as predicted palindromic thyroid hormone response elements (ppTREs); the region focused upon in this study is distinguished as ppTRE2.A zebrafish promoter-reporter construct was developed by deleting a 25bp sequence containing ppTRE2 (ΔppTRE2). Then transgenic larvae were treated with triiodothyronine (T3) to observe reporter expression. Results suggested that ppTRE2 is necessary for increased expression of lws1 when exogenous TH is added.
In this study, we sought to further validate this finding, and ablated the thyroids of ΔppTRE2 zebrafish using a genetic/pharmacological approach. The experimental outcomes suggested the same conclusion as prior findings – ppTRE2 is necessary for the endogenous suppression of lws1 in embryos and for the upregulation of lws1 and downregulation of lws2 in response to increased TH.
Funding: This project was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grant #P20GM103408.