Abstract
Human long and medium wavelength-sensitive (LWS/MWS) opsins arose from a tandem duplication event resulting in opsins with divergent spectral sensitivities. Zebrafish independently underwent tandem duplication of their lws opsin, resulting in two spectrally divergent genes, lws1/lws2. Thyroid hormone (TH) differentially regulates these opsins; increased TH causes an increase in lws1 expression at the expense of lws2 (“opsin switching”). Here we investigate a cis-regulatory sequence that may mediate the response to TH using promoter-reporter analysis in transgenic zebrafish. We show that the 2.6-kb region upstream of lws1 combined with the 1.8-kb intergenic region are sufficient for typical lws1/2 expression and regulation by TH. We identify the 0.6-kb region upstream of lws1, as the likely region of TH-responsive cis-regulatory elements and use genomic prediction tools to uncover a putative lws regulatory element (LRE), in this 0.6-kb region. When we disrupt the LRE, we find that in larvae, lws1 reporter is prematurely expressed and does not respond to TH, and lws2 reporter increases in response to TH. In juveniles and adults, however, the patterning of lws1/2 reporters largely resembles stereotypical lws1/2 expression. Therefore, the LRE appears to be involved in differential expression of lws opsins and their response to TH during development.
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Acknowledgements
This work was supported by NIH R01 EY012146 (DLS) and NIH P20 GM103408 (Idaho INBRE) and by Grants-in-Aid for Scientific Research (A) (15H02421 and 18H04005) and (B) (23K27252) from the Japan Society for the Promotion of Science (JSPS) to SK. The authors thank Dr. David Parichy for the Tg(tg: nVenus-2a-nfnB)wp.rt8 transgenic line, Audrey Duncan for technical assistance, Ruth Frey and the staff of the UI Laboratory Animal Research Facility for zebrafish care, and Onesmo Balemba and Raquel Simao Gurge of the UI Imaging and Data Acquisition Core (IDAC). The IDAC is administered by the Institute for Modeling Collaboration and Innovation, supported by NIH P20 GM104420. We thank members of the Mitchell and Stenkamp labs for helpful discussions of the project.
Funding
This work received funding from NIH R01 EY012146 (DLS), NIH P20 GM103408 (Idaho INBRE), and NIH P20 GM104420 (DLS), and through Grants-in-Aid for Scientific Research (A) (15H02421 and 18H04005) and (B) (23K27252) from the Japan Society for the Promotion of Science (JSPS) to SK.
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Data acquisition: L.B., R.M., I.K., R.A., B.T., H.P. All authors assisted with data analysis and interpretation. L.B. and R.M. generated figures. L.B., R.M., S.K., and D.S. conceived the project and wrote the manuscript.
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Barrett, L.M., Mackin, R.D., Ashino, R. et al. A potential cis-regulatory element regulates differential expression of long wavelength-sensitive opsins in zebrafish. Sci Rep (2026). https://doi.org/10.1038/s41598-026-47667-4
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DOI: https://doi.org/10.1038/s41598-026-47667-4