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Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
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Retinoic Acid-Regulated Epigenetic Marks Identify Alx1 as a Direct Target Gene Required for Optic Cup Formation
Marie Berenguer1,2, Gregg Duester1
1Development, Aging, and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Genes
|September 27, 2025
Summary
Retinoic acid (RA) directly activates the Alx1 gene, which is crucial for optic cup formation during early eye development. Loss of Alx1 disrupts perioptic mesenchyme migration, impairing optic cup development in embryos.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Retinoic acid (RA) is a key transcriptional regulator in eye development, essential for optic vesicle to optic cup formation.
- Identifying direct RA target genes involved in this process has been challenging due to the widespread effects of RA synthesis loss.
Purpose of the Study:
- To identify direct target genes of retinoic acid (RA) involved in optic cup formation.
- To elucidate the molecular mechanisms by which RA regulates early eye development.
Main Methods:
- Combined ChIP-seq for H3K27ac and RNA-seq on optic field tissue from wild-type and Rdh10-/- embryos.
- Utilized in situ hybridization and CRISPR/Cas9 gene editing to validate gene function and expression.
Main Results:
- Identified Alx1 as a direct RA target gene, showing decreased expression and H3K27ac marks in Rdh10-/- embryos.
- Demonstrated that Alx1 knockout leads to optic cup formation defects due to impaired perioptic mesenchyme migration.
Conclusions:
- RA directly activates Alx1 in perioptic mesenchyme, promoting optic cup formation.
- Alx1 plays a critical role in the separation of optic cup epithelium and forebrain neuroepithelium during early eye development.
