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
  • Receptors, Thyroid Hormone/physiology*
  • Animals
  • Zebrafish
  • Gene Deletion
  • Retinal Cone Photoreceptor Cells
  • Opsins/genetics
  • Opsins/metabolism*
  • Gene Expression Regulation
  • Ultraviolet Rays
  • Cytochrome P-450 Enzyme System/genetics
  • Cytochrome P-450 Enzyme System/metabolism*
  • Color Vision/genetics
  • Color Vision/physiology*
  • Visual Perception/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
(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.
Genes / Markers
Figures
No images available
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WTchemical treatment by environment: thyroid hormoneAdult
WTchemical treatment by environment: thyroid hormoneAdult
thraavp33rc1/vp33rc1chemical treatment by environment: thyroid hormoneAdult
thraavp33rc1/vp33rc1chemical treatment by environment: thyroid hormoneAdult
thraavp33rc1/vp33rc1; thrabvp31rc1/vp31rc1chemical treatment by environment: thyroid hormoneAdult
thraavp33rc1/vp33rc1; thrabvp31rc1/vp31rc1chemical treatment by environment: thyroid hormoneAdult
thraavp33rc1/vp33rc1; thrabvp31rc1/vp31rc1; thrbstl627/stl627chemical treatment by environment: thyroid hormoneAdult
thraavp33rc1/vp33rc1; thrabvp31rc1/vp31rc1; thrbstl627/stl627chemical treatment by environment: thyroid hormoneAdult
thraavp33rc1/vp33rc1; thrbstl627/stl627chemical treatment by environment: thyroid hormoneAdult
thraavp33rc1/vp33rc1; thrbstl627/stl627chemical treatment by environment: thyroid hormoneAdult
1 - 10 of 33
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b4
    Insertion
    jh1TgTransgenic Insertion
      kj9TgTransgenic Insertion
        q22TgTransgenic Insertion
          stl627
            Small Deletion
            stl628
              Small Deletion
              vp31rc1
                Small Deletion
                vp33rc1
                  Small Deletion
                  1 - 8 of 8
                  Show
                  Human Disease / Model
                  No data available
                  Sequence Targeting Reagents
                  Target Reagent Reagent Type
                  thrbCRISPR2-thrbCRISPR
                  thrbCRISPR5-thrbCRISPR
                  thrbCRISPR6-thrbCRISPR
                  1 - 3 of 3
                  Show
                  Fish
                  Antibodies
                  Orthology
                  Engineered Foreign Genes
                  Marker Marker Type Name
                  EGFPEFGEGFP
                  TomatoEFGTomato
                  1 - 2 of 2
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                  Mapping