ArticleStem cell reports2025
Human macula formation involves two waves of retinoic acid suppression via CYP26A1 that modulate cell cycle exit and cone subtype specification.
Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Photoreceptor replacement: a disease-agnostic approach for the treatment of advanced retinal degeneration.Eye (London, England) · 2026Review
- Genome-wide association and multi-omics functional screens reveal the genetic architecture of foveal development.medRxiv : the preprint server for health sciences · 2026Article
- Convergent re-evolution of CNS structures: focus on the fovea.Current opinion in genetics & development · 2026Review
- Bilateral bifoveate retina in a human resembling lizard foveal architecture.Ophthalmic genetics · 2026Article
- A cell fate specification and transition mechanism for human foveolar cone subtype patterning.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
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Authors and funding
5 authors.
Funding
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Abstract
The human macula is a specialized, cone-rich region of the eye, critical for high-acuity vision, yet the pathways regulating its development remain poorly understood. RA-catabolizing enzyme CYP26A1 establishes the chick high-acuity area via upregulation of fibroblast growth factor 8 (FGF8). However, detailed analysis of this pathway and its functions has not been performed in early human fetal tissue. Fluorescent in situ hybridization revealed striking biphasic CYP26A1 expression but little FGF8 in the presumptive macula region between post-conception weeks (PCW) 6-17. Pharmacological retinoic acid (RA) signaling inhibition in human retinal organoids mimicking the two waves of CYP26A1 revealed early RA inhibition prompted early cell cycle exit and increased cone genesis, while late inhibition altered cone subtype specification. Conversely, recombinant FGF8 had no effect on photoreceptor fate. This work provides spatiotemporal examination of CYP26A1 across human macular development, as well as experimental evidence for the different roles of RA signaling inhibition in a human model of retinal development.
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Registered trials
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