Biliverdin regulates NR2E3 and zebrafish retinal photoreceptor development
Blaine Connor1, Kayla Titialii-Torres2, Abigail E Rockenhaus3
1Department of Biology, Johns Hopkins University, Baltimore, MD, 21218, USA.
Scientific Reports
|May 4, 2022
Summary
Biliverdin, a heme breakdown product, acts as a small molecule ligand for the NR2E3 receptor. This interaction is crucial for normal retinal photoreceptor development and maintenance in zebrafish.
Area of Science:
- Molecular Biology
- Developmental Biology
- Ophthalmology
Background:
- NR2E3 is an orphan nuclear receptor critical for retinal photoreceptor development.
- Loss-of-function mutations in NR2E3 lead to retinal degeneration.
- Endogenous ligands for NR2E3 remain unidentified, hindering understanding of its regulation.
Purpose of the Study:
- To identify endogenous small molecule ligands that regulate NR2E3.
- To investigate the role of identified ligands in retinal development and maintenance.
- To explore the connection between heme metabolism and NR2E3 function.
Main Methods:
- Ligand binding assays using retinal extracts and purified NR2E3.
- Reporter gene assays to measure NR2E3 transcriptional activity.
- Zebrafish models to assess the impact of biliverdin synthesis inhibition and supplementation on photoreceptor development.
Main Results:
- Biliverdin specifically binds to the ligand-binding domain of NR2E3.
- Biliverdin induces NR2E3-dependent reporter gene expression.
- Inhibition of biliverdin synthesis impairs zebrafish photoreceptor development, a phenotype rescued by exogenous biliverdin.
Conclusions:
- Biliverdin is identified as an endogenous small molecule ligand for NR2E3.
- Biliverdin is essential for proper retinal photoreceptor development in zebrafish.
- Heme metabolism may play a regulatory role in photoreceptor cell development via NR2E3.
