ZFIN ID: ZDB-PUB-200617-12
Thyroid hormone receptors mediate two distinct mechanisms of long-wavelength vision
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.
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
Microarrays: GEO:GSE143312
MeSH Terms:
  • Animals
  • Color Vision/genetics
  • Color Vision/physiology*
  • Cytochrome P-450 Enzyme System/genetics
  • Cytochrome P-450 Enzyme System/metabolism*
  • Gene Deletion
  • Gene Expression Regulation
  • Opsins/genetics
  • Opsins/metabolism*
  • Receptors, Thyroid Hormone/physiology*
  • Retinal Cone Photoreceptor Cells
  • Ultraviolet Rays
  • Visual Perception/physiology*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 32541022 Full text @ Proc. Natl. Acad. Sci. USA
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.