ArticleProceedings of the National Academy of Sciences of the United States of America2012
Forkhead box transcription factor FoxC1 preserves corneal transparency by regulating vascular growth.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 99 citations in OpenAlex.
- Article
- FOXC1 Regulates Cytokine Signaling, Inflammatory Pathways, and Retinoid Metabolism to Maintain Limbal Epithelial Cell Homeostasis In Vitro.International journal of molecular sciences · 2026Article
- miRNA Expression Profile in Primary Limbal Epithelial Cells of Aniridia Patients.Investigative ophthalmology & visual science · 2025Article
- Neutrophil pyroptosis regulates corneal wound healing and post-injury neovascularisation.Clinical and translational medicine · 2024Article
- Diagnostic Challenges of Axenfeld-Rieger Syndrome and a Novel FOXC1 Gene Mutation in a Polish Family.Journal of clinical medicine · 2024Article
- Pleiotropy in FOXC1-attributable phenotypes involves altered ciliation and cilia-dependent signaling.Scientific reports · 2024Article
- Article
- Primary Cilium in Neural Crest Cells Crucial for Anterior Segment Development and Corneal Avascularity.Investigative ophthalmology & visual science · 2024Article
- The Secreted Ly6/uPAR-Related Protein 1 (Slurp1) Modulates Corneal Angiogenic Inflammation Via NF-κB Signaling.Investigative ophthalmology & visual science · 2024Article
- Article
- Identification of the regulatory circuit governing corneal epithelial fate determination and disease.PLoS biology · 2023Article
- FoxC1 activates limbal epithelial stem cells following corneal epithelial debridement.Experimental eye research · 2023Article
- Differential roles of FOXC2 in the trabecular meshwork and Schlemm's canal in glaucomatous pathology.Life science alliance · 2023Article
- Loss of FOXC1 contributes to the corneal epithelial fate switch and pathogenesis.Signal transduction and targeted therapy · 2021Article
- Disruption of foxc1 genes in zebrafish results in dosage-dependent phenotypes overlapping Axenfeld-Rieger syndrome.Human molecular genetics · 2020Article
- Organogenesis and distribution of the ocular lymphatic vessels in the anterior eye.JCI insight · 2020Article
- Emerging insights from the genetics of cerebral small-vessel disease.Annals of the New York Academy of Sciences · 2020Review
- Tissue Engineering of Axially Vascularized Soft-Tissue Flaps with a Poly-(ɛ-Caprolactone) Nanofiber-Hydrogel Composite.Advances in wound care · 2020Article
- Conditional inactivation of Foxc1 and Foxc2 in neural crest cells leads to cardiac abnormalities.Genesis (New York, N.Y. : 2000) · 2020Article
- The Ocular Neural Crest: Specification, Migration, and Then What?Frontiers in cell and developmental biology · 2020Review
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10 authors at 3 institutions in 3 countries.
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Abstract
Normal vision requires the precise control of vascular growth to maintain corneal transparency. Here we provide evidence for a unique mechanism by which the Forkhead box transcription factor FoxC1 regulates corneal vascular development. Murine Foxc1 is essential for development of the ocular anterior segment, and in humans, mutations have been identified in Axenfeld-Rieger syndrome, a disorder characterized by anterior segment dysgenesis. We show that FOXC1 mutations also lead to corneal angiogenesis, and that mice homozygous for either a global (Foxc1(-/-)) or neural crest (NC)-specific (NC-Foxc1(-/-)) null mutation display excessive growth of corneal blood and lymphatic vessels. This is associated with disorganization of the extracellular matrix and increased expression of multiple matrix metalloproteinases. Heterozygous mutants (Foxc1(+/-) and NC-Foxc1(+/-)) exhibit milder phenotypes, such as disrupted limbal vasculature. Moreover, environmental exposure to corneal injury significantly increases growth of both blood and lymphatic vessels in both Foxc1(+/-) and NC-Foxc1(+/-) mice compared with controls. Notably, this amplification of the angiogenic response is abolished by inhibition of VEGF receptor 2. Collectively, these findings identify a role for FoxC1 in inhibiting corneal angiogenesis, thereby maintaining corneal transparency by regulating VEGF signaling.
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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.