PUBLICATION

Thyroid hormone receptors mediate two distinct mechanisms of long-wavelength vision

Authors
Volkov, L.I., Kim-Han, J.S., Saunders, L.M., Poria, D., Hughes, A.E.O., Kefalov, V.J., Parichy, D.M., Corbo, J.C.
ID
ZDB-PUB-200617-12
Date
2020
Source
Proceedings of the National Academy of Sciences of the United States of America   117(26): 15262-15269 (Journal)
Registered Authors
Corbo, Joseph, Parichy, David M., Volkov, Leo
Keywords
cone photoreceptors, retinal development, thyroid hormone, vitamin A2, zebrafish
Datasets
GEO:GSE143312
MeSH Terms
  • Ultraviolet Rays
  • Gene Deletion
  • Animals
  • Receptors, Thyroid Hormone/physiology*
  • Opsins/genetics
  • Opsins/metabolism*
  • Gene Expression Regulation
  • Cytochrome P-450 Enzyme System/genetics
  • Cytochrome P-450 Enzyme System/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Retinal Cone Photoreceptor Cells
  • Visual Perception/physiology*
  • Zebrafish
  • Color Vision/genetics
  • Color Vision/physiology*
(all 16)
PubMed
32541022 Full text @ Proc. Natl. Acad. Sci. USA
Abstract
Thyroid hormone (TH) signaling plays an important role in the regulation of long-wavelength vision in vertebrates. In the retina, thyroid hormone receptor β (thrb) is required for expression of long-wavelength-sensitive opsin (lws) in red cone photoreceptors, while in retinal pigment epithelium (RPE), TH regulates expression of a cytochrome P450 enzyme, cyp27c1, that converts vitamin A1 into vitamin A2 to produce a red-shifted chromophore. To better understand how TH controls these processes, we analyzed the phenotype of zebrafish with mutations in the three known TH nuclear receptor transcription factors (thraa, thrab, and thrb). We found that no single TH nuclear receptor is required for TH-mediated induction of cyp27c1 but that deletion of all three (thraa-/-;thrab-/-;thrb-/- ) completely abrogates its induction and the resulting conversion of A1- to A2-based retinoids. In the retina, loss of thrb resulted in an absence of red cones at both larval and adult stages without disruption of the underlying cone mosaic. RNA-sequencing analysis revealed significant down-regulation of only five genes in adult thrb-/- retina, of which three (lws1, lws2, and miR-726) occur in a single syntenic cluster. In the thrb-/- retina, retinal progenitors destined to become red cones were transfated into ultraviolet (UV) cones and horizontal cells. Taken together, our findings demonstrate cooperative regulation of cyp27c1 by TH receptors and a requirement for thrb in red cone fate determination. Thus, TH signaling coordinately regulates both spectral sensitivity and sensory plasticity.
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Citation
Volkov, L.I., Kim-Han, J.S., Saunders, L.M., Poria, D., Hughes, A.E.O., Kefalov, V.J., Parichy, D.M., Corbo, J.C. (2020) Thyroid hormone receptors mediate two distinct mechanisms of long-wavelength vision. Proceedings of the National Academy of Sciences of the United States of America. 117(26):15262-15269.