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

Show all Figures

Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment by environment: thyroid hormone	Adult	eye cyp27c1 expression increased amount, abnormal	Fig. 2
WT	chemical treatment by environment: thyroid hormone	Adult	eye all-trans-3,4-didehydroretinol increased amount, abnormal	Fig. 2
thraa^{vp33rc1/vp33rc1}	chemical treatment by environment: thyroid hormone	Adult	eye cyp27c1 expression increased amount, abnormal	Fig. 2
thraa^{vp33rc1/vp33rc1}	chemical treatment by environment: thyroid hormone	Adult	eye all-trans-3,4-didehydroretinol increased amount, abnormal	Fig. 2
thraa^{vp33rc1/vp33rc1}; thrab^{vp31rc1/vp31rc1}	chemical treatment by environment: thyroid hormone	Adult	eye cyp27c1 expression increased amount, abnormal	Fig. 2
thraa^{vp33rc1/vp33rc1}; thrab^{vp31rc1/vp31rc1}	chemical treatment by environment: thyroid hormone	Adult	eye all-trans-3,4-didehydroretinol increased amount, abnormal	Fig. 2
thraa^{vp33rc1/vp33rc1}; thrab^{vp31rc1/vp31rc1}; thrb^{stl627/stl627}	chemical treatment by environment: thyroid hormone	Adult	eye cyp27c1 expression amount, ameliorated	Fig. 2
thraa^{vp33rc1/vp33rc1}; thrab^{vp31rc1/vp31rc1}; thrb^{stl627/stl627}	chemical treatment by environment: thyroid hormone	Adult	eye all-trans-3,4-didehydroretinol normal amount, ameliorated	Fig. 2
thraa^{vp33rc1/vp33rc1}; thrb^{stl627/stl627}	chemical treatment by environment: thyroid hormone	Adult	eye cyp27c1 expression increased amount, abnormal	Fig. 2
thraa^{vp33rc1/vp33rc1}; thrb^{stl627/stl627}	chemical treatment by environment: thyroid hormone	Adult	eye all-trans-3,4-didehydroretinol increased amount, ameliorated	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
b4		Insertion	slc45a2
jh1Tg	Tg(ptf1a:EGFP)	Transgenic Insertion
kj9Tg	Tg(-5.5opn1sw1:EGFP)	Transgenic Insertion
q22Tg	Tg(thrb:Tomato)	Transgenic Insertion
stl627		Small Deletion	thrb
stl628		Small Deletion	thrb
vp31rc1		Small Deletion	thrab
vp33rc1		Small Deletion	thraa

1 - 8 of 8

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
thrb	CRISPR2-thrb	CRISPR
thrb	CRISPR5-thrb	CRISPR
thrb	CRISPR6-thrb	CRISPR

Fish

Fish
q22Tg
thraa^{vp33rc1/vp33rc1}
thraa^{vp33rc1/vp33rc1}; thrab^{vp31rc1/vp31rc1}
thraa^{vp33rc1/vp33rc1}; thrab^{vp31rc1/vp31rc1}; thrb^{stl627/stl627}
thraa^{vp33rc1/vp33rc1}; thrb^{stl627/stl627}
thrab^{vp31rc1/vp31rc1}
thrab^{vp31rc1/vp31rc1}; thrb^{stl627/stl627}
thrb^{stl627/stl627}
thrb^{stl627/stl627}; q22Tg
WT

1 - 10 of 10

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Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP
Tomato	EFG	Tomato

Mapping

Volkov et al., 2020 ZDB-PUB-200617-12 PMID:32541022

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

Volkov et al., 2020

ZDB-PUB-200617-12
PMID:32541022