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Updated: Jun 21, 2025
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Vibratome Sectioning Mouse Retina to Prepare Photoreceptor Cultures
Published on: December 22, 2014
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Evolutionary conservation of VSX2 super-enhancer modules in retinal development
Victoria Honnell1, Shannon Sweeney1, Jackie Norrie1
1Department of Developmental Neurobiology at St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Development (Cambridge, England)
|July 12, 2024
Summary
Super-enhancers (SEs) control cell identity. Human VSX2 SE modules show specific activity, rescuing microphthalmia in mice and revealing roles in retinal organoid development and bipolar neuron formation.
Area of Science:
- Genomics
- Developmental Biology
- Ophthalmology
Background:
- Super-enhancers (SEs) are crucial genomic regions regulating cell identity and fate.
- Developmental stage- and cell type-specific modules within the murine Vsx2 SE were previously identified.
Purpose of the Study:
- To investigate the function and conserved activity of human VSX2 SE modules in retinal development.
- To model human retinal development and disease using stem cell-derived organoids.
Main Methods:
- Reporter gene assays to assess human VSX2 SE module activity.
- Gene editing (CRISPR-Cas9) to delete SE modules in human embryonic stem cells.
- Generation of human retinal organoids for functional analysis.
Main Results:
- Human VSX2 SE modules exhibit conserved developmental stage- and cell type-specific activity.
- Insertion of a human VSX2 SE module rescued the microphthalmia phenotype in mice.
- Deletion of specific modules in human retinal organoids led to reduced organoid size and impaired bipolar neuron development.
Conclusions:
- The human VSX2 SE is a prototypical model for studying complex gene regulation in neurogenesis.
- Dysregulation of VSX2 SE modules may contribute to human eye developmental disorders and phenotypic diversity.
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