ArticlePLoS genetics2012
Vsx2 controls eye organogenesis and retinal progenitor identity via homeodomain and non-homeodomain residues required for high affinity DNA binding.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 66 citations in OpenAlex.
- Multi-organ imaging and genetics show the impact of sleep patterns on the human brain and body.Communications medicine · 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
- Rare heterozygous missense variants in VSX2 are associated with retinal detachment.PLoS genetics · 2026Article
- Article
- Genotypic and phenotypic spectrum of anophthalmia/microphthalmia in families from Khyber Pakhtunkhwa, Pakistan.Journal of human genetics · 2025Article
- Modeling combinatorial regulation from single-cell multi-omics provides regulatory units underpinning cell type landscape using cRegulon.Genome biology · 2025Article
- SOX2-VSX2 Co-Occupancy Shapes Retinal Neurogenesis Through Dynamic Chromatin Regulation.bioRxiv : the preprint server for biology · 2025Article
- Expression status transition ofF1000Research · 2025Article
- SOX2-driven enhancer landscape defines the transcriptional architecture of retinogenesis.Development (Cambridge, England) · 2024Article
- Single-cell transcriptomics reveals the molecular basis of human iPS cell differentiation into ectodermal ocular lineages.Communications biology · 2024Article
- Microphthalmia and disrupted retinal development due to abioRxiv : the preprint server for biology · 2024Article
- Evolutionary conservation of VSX2 super-enhancer modules in retinal development.Development (Cambridge, England) · 2024Article
- Human Pluripotent Stem Cell-Derived Retinal Organoids: A Viable Platform for Investigating the Efficacy of Adeno-Associated Virus Gene Therapy.International journal of stem cells · 2024Article
- Microphthalmia and Disrupted Retinal Development Due to aEye and brain · 2024Article
- A framework to identify functional interactors that contribute to disrupted early retinal development in Vsx2 ocular retardation J mice.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
- Chromatin accessibility-based characterisation of brain gene regulatory networks in three distinct honey bee polyphenisms.Nucleic acids research · 2022Article
- Involvement of a Basic Helix-Loop-Helix GeneJournal of developmental biology · 2022Article
- Functional analysis of the Vsx2 super-enhancer uncovers distinct cis-regulatory circuits controlling Vsx2 expression during retinogenesis.Development (Cambridge, England) · 2022Article
- Analysis of gene network bifurcation during optic cup morphogenesis in zebrafish.Nature communications · 2021Article
- Generation and Staging of Human Retinal Organoids Based on Self-Formed Ectodermal Autonomous Multi-Zone System.Frontiers in cell and developmental biology · 2021Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
The homeodomain and adjacent CVC domain in the visual system homeobox (VSX) proteins are conserved from nematodes to humans. Humans with missense mutations in these regions of VSX2 have microphthalmia, suggesting both regions are critical for function. To assess this, we generated the corresponding mutations in mouse Vsx2. The homeodomain mutant protein lacked DNA binding activity and the knock-in mutant phenocopied the null mutant, ocular retardation J. The CVC mutant protein exhibited weakened DNA binding; and, although the corresponding knock-in allele was recessive, it unexpectedly caused the strongest phenotype, as indicated by severe microphthalmia and hyperpigmentation of the neural retina. This occurred through a cryptic transcriptional feedback loop involving the transcription factors Mitf and Otx1 and the Cdk inhibitor p27(Kip1). Our data suggest that the phenotypic severity of the CVC mutant depends on the weakened DNA binding activity elicited by the CVC mutation and a previously unknown protein interaction between Vsx2 and its regulatory target Mitf. Our data also suggest that an essential function of the CVC domain is to assist the homeodomain in high-affinity DNA binding, which is required for eye organogenesis and unhindered execution of the retinal progenitor program in mammals. Finally, the genetic and phenotypic behaviors of the CVC mutation suggest it has the characteristics of a recessive neomorph, a rare type of genetic allele.
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