ArticleProceedings of the National Academy of Sciences of the United States of America2015
Two transcription factors, Pou4f2 and Isl1, are sufficient to specify the retinal ganglion cell fate.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 115 citations in OpenAlex.
- Lineage Tracing Reveals atoh7-Positive and Negative Retinal Ganglion Cell Populations in the Zebrafish Retina.Investigative ophthalmology & visual science · 2026Article
- Single-cell analysis reveals cellular heterogeneity and limits of marker-based assessment in retinal ganglion cell-enriched organoid cultures.Molecular medicine (Cambridge, Mass.) · 2026Article
- Identification of transgene insertion sites via short- and long-read whole genome sequencing.bioRxiv : the preprint server for biology · 2026Article
- Tbr2-dependent parallel pathways regulate the development of distinct ipRGC subtypes.Communications biology · 2026Article
- Human pluripotent stem cell-derived retinal ganglion cells: advances in differentiation and translational applications.Molecular medicine (Cambridge, Mass.) · 2025Review
- Multi-omics reveals cross-tissue regulatory mechanisms of autism risk loci via gut microbiota-immunity-brain axis.AMB Express · 2025Article
- Transcriptomics of Various Diseases Reveals the Core Role of Immune System Pathways in Retinal Damage Repair and Nerve Regeneration.Molecular neurobiology · 2025Article
- Influences of lead-based perovskite nanoparticles exposure on early development of human retina.Journal of nanobiotechnology · 2025Article
- A large-scale CRISPR screen reveals context-specific genetic regulation of retinal ganglion cell regeneration.Development (Cambridge, England) · 2024Article
- A cis-regulatory module underlies retinal ganglion cell genesis and axonogenesis.Cell reports · 2024Article
- Article
- Rapid and efficient generation of a transplantable population of functional retinal ganglion cells from fibroblasts.Cell proliferation · 2024Article
- Intrinsic and Induced Neuronal Regeneration in the Mammalian Retina.Antioxidants & redox signaling · 2023Review
- Human retinal ganglion cell neurons generated by synchronous BMP inhibition and transcription factor mediated reprogramming.NPJ Regenerative medicine · 2023Article
- Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium.Molecular neurodegeneration · 2023Review
- InducibleCells · 2023Article
- Comparative expression analysis of the Atoh7 gene regulatory network in the mouse and chicken auditory hindbrain.Cell and tissue research · 2023Article
- Key transcription factors influence the epigenetic landscape to regulate retinal cell differentiation.Nucleic acids research · 2023Article
- Neurog2 regulates Isl1 to modulate horizontal cell number.Development (Cambridge, England) · 2023Article
- Signaling - transcription interactions in mouse retinal ganglion cells early axon pathfinding -a literature review.Frontiers in ophthalmology · 2023Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
As with other retinal cell types, retinal ganglion cells (RGCs) arise from multipotent retinal progenitor cells (RPCs), and their formation is regulated by a hierarchical gene-regulatory network (GRN). Within this GRN, three transcription factors--atonal homolog 7 (Atoh7), POU domain, class 4, transcription factor 2 (Pou4f2), and insulin gene enhancer protein 1 (Isl1)--occupy key node positions at two different stages of RGC development. Atoh7 is upstream and is required for RPCs to gain competence for an RGC fate, whereas Pou4f2 and Isl1 are downstream and regulate RGC differentiation. However, the genetic and molecular basis for the specification of the RGC fate, a key step in RGC development, remains unclear. Here we report that ectopic expression of Pou4f2 and Isl1 in the Atoh7-null retina using a binary knockin-transgenic system is sufficient for the specification of the RGC fate. The RGCs thus formed are largely normal in gene expression, survive to postnatal stages, and are physiologically functional. Our results indicate that Pou4f2 and Isl1 compose a minimally sufficient regulatory core for the RGC fate. We further conclude that during development a core group of limited transcription factors, including Pou4f2 and Isl1, function downstream of Atoh7 to determine the RGC fate and initiate RGC differentiation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.