ArticleMolecular vision2012
Interaction between hedgehog signalling and PAX6 dosage mediates maintenance and regeneration of the corneal epithelium.
Article in Molecular vision, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Activated Hedgehog signaling in keratocytes leads to stromal stiffness and impairs corneal regeneration.NPJ Regenerative medicine · 2026Article
- Review
- Spatial correlations constrain cellular lifespan and pattern formation in corneal epithelium homeostasis.eLife · 2021Article
- Epithelial WNT2B and Desert Hedgehog Are Necessary for Human Colonoid Regeneration after Bacterial Cytotoxin Injury.iScience · 2020Article
- Article
- The hedgehog pathway and ocular developmental anomalies.Human genetics · 2019Review
- In vivo imaging of epithelial wound healing in the cnidarian Clytia hemisphaerica demonstrates early evolution of purse string and cell crawling closure mechanisms.BMC developmental biology · 2017Article
- Sonic hedgehog (SHH) signaling improves the angiogenic potential of Wharton's jelly-derived mesenchymal stem cells (WJ-MSC).Stem cell research & therapy · 2017Article
- Lacrimal Gland Repair Using Progenitor Cells.Stem cells translational medicine · 2017Article
- The core planar cell polarity gene,Royal Society open science · 2016Article
- PAX6, brain structure and function in human adults: advanced MRI in aniridia.Annals of clinical and translational neurology · 2016Article
- Ocular surface development and gene expression.Journal of ophthalmology · 2013Article
- Differentiation of human amniotic epithelial cells into corneal epithelial-like cells in vitro.International journal of ophthalmology · 2013Article
- Stem cells and corneal epithelial maintenance: insights from the mouse and other animal models.Results and problems in cell differentiation · 2012Review
- Corneal epithelial development and homeostasis.Differentiation; research in biological diversityReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo investigate the roles of intracellular signaling elicited by Hedgehog (Hh) ligands in corneal maintenance and wound healing.
methodsThe expression of Hedgehog pathway components in the cornea was assayed by immunohistochemistry, western blot and reverse-transcription polymerase chain reaction (RT-PCR), in wild-type mice and mice that were heterozygous null for the gene encoding the transcription factor, paired box gene 6 (Pax6). Corneal epithelial wound healing and cell migration assays were performed after pharmacological upregulation and downregulation of the hedgehog pathway. Reporter mice, mosaic for expression of the gene encoding β-galactosidase (LacZ), were crossed to Pax6(+/-) mice, mice heterozygous for the gene encoding GLI-Kruppel family member GLI3, and Pax6(+/-)Gli3(+/-) double heterozygotes, to assay patterns of cell migration and corneal epithelial organization in vivo.
resultsCorneal epithelial wound healing rates increased in response to application of Sonic hedgehog (Shh), but only in mice with wild-type Pax6 dosage. Downregulation of Hedgehog signalling inhibited corneal epithelial cell proliferation. Pax6(+/-) corneal epithelia showed increased proliferation in response to exogenous Shh, but not increased migration. Desert hedgehog (Dhh) was shown to be the major endogenous ligand, with Shh detectable only by RT-PCR and only after epithelial wounding. The activity of phosphatidylinositol-3-OH kinase-γ (PI3Kγ) was not required for the increased migration response in response to Shh. Nuclear expression of the activator form of the transcription factor Gli3 (which mediates Hh signalling) was reduced in Pax6(+/-) corneal epithelia. Pax6(+/-)Gli3(+/-) double heterozygotes showed highly disrupted patterns of clonal arrangement of cells in the corneal epithelium.
conclusionsThe data show key roles for endogenous Dhh signalling in maintenance and regeneration of the corneal epithelium, demonstrate an interaction between Pax6 and Hh signalling in the corneal epithelium, and show that failure of Hh signalling pathways is a feature of Pax6(+/-) corneal disease that cannot be remedied pharmacologically by addition of the ligands.
Indexed as
Identifiers
22275805PMC3265179W2108972628What OpenQuestion holds
Registered trials
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.