PUBLICATION

Biliverdin regulates NR2E3 and zebrafish retinal photoreceptor development

Authors
Connor, B., Titialii-Torres, K., Rockenhaus, A.E., Passamonte, S., Morris, A.C., Lee, Y.S.
ID
ZDB-PUB-220506-12
Date
2022
Source
Scientific Reports   12: 7310 (Journal)
Registered Authors
Morris, Ann C., Titialii-Torres, Kayla
Keywords
none
MeSH Terms
  • Photoreceptor Cells, Vertebrate/metabolism
  • Photoreceptor Cells/metabolism
  • Receptors, Cytoplasmic and Nuclear
  • Retinal Degeneration*/metabolism
  • Animals
  • Heme
  • Zebrafish*/metabolism
  • Ligands
  • Zebrafish Proteins/genetics
  • Orphan Nuclear Receptors/genetics
  • Biliverdine
(all 11)
PubMed
35508617 Full text @ Sci. Rep.
Abstract
NR2E3 is an orphan nuclear receptor whose loss-of-function causes abnormal retinal photoreceptor development and degeneration. However, despite that many nuclear receptors are regulated by binding of small molecule ligands, biological small molecule ligands regulating NR2E3 have not been identified. Identification of an endogenous NR2E3 ligand might reveal a previously unrecognized component contributing to retinal development and maintenance. Here we report that biliverdin, a conserved green pigment from heme catabolism, regulates NR2E3 and is necessary for zebrafish retinal photoreceptor development. Biliverdin from retinal extracts specifically bound to NR2E3's ligand-binding domain and induced NR2E3-dependent reporter gene expression. Inhibition of biliverdin synthesis decreased photoreceptor cell populations in zebrafish larvae, and this phenotype was alleviated by exogenously supplied biliverdin. Thus, biliverdin is an endogenous small molecule ligand for NR2E3 and a component necessary for the proper development of photoreceptor cells. This result suggests a possible role of heme metabolism in the regulation of retinal photoreceptor cell development.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
fl1TgTransgenic Insertion
    1 - 1 of 1
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    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    No data available
    Fish
    Fish
    fl1Tg
    1 - 1 of 1
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    Antibodies
    Orthology
    Gene Orthology
    nr2e3
    1 - 1 of 1
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    Engineered Foreign Genes
    Marker Marker Type Name
    EGFPEFGEGFP
    1 - 1 of 1
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    Mapping
    No data available