ArticlePloS one2014
A role for smoothened during murine lens and cornea development.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Conservation of Epithelial-to-Mesenchymal Transition Process in Neural Crest Cells and Metastatic Cancer.Cells, tissues, organs · 2021Pooled it
- Activated Hedgehog signaling in keratocytes leads to stromal stiffness and impairs corneal regeneration.NPJ Regenerative medicine · 2026Article
- Construction and Identification of a Novel Mice Model of Microphthalmia.Translational vision science & technology · 2024Article
- TOB1 and TOB2 mark distinct RNA processing granules in differentiating lens fiber cells.Journal of molecular histology · 2024Article
- Aniridia-related keratopathy relevant cell signaling pathways in human fetal corneas.Histochemistry and cell biology · 2022Article
- Review
- Changes in DNA methylation hallmark alterations in chromatin accessibility and gene expression for eye lens differentiation.Epigenetics & chromatin · 2022Article
- Article
- Bi-allelic Variations of SMO in Humans Cause a Broad Spectrum of Developmental Anomalies Due to Abnormal Hedgehog Signaling.American journal of human genetics · 2020Article
- Metabolic and pathologic profiles of human LSS deficiency recapitulated in mice.PLoS genetics · 2020Article
- Genetics of anophthalmia and microphthalmia. Part 2: Syndromes associated with anophthalmia-microphthalmia.Human genetics · 2019Review
- Zebrafish mab21l2 mutants possess severe defects in optic cup morphogenesis, lens and cornea development.Developmental dynamics : an official publication of the American Association of Anatomists · 2019Article
- The core planar cell polarity gene, Vangl2, maintains apical-basal organisation of the corneal epithelium.Journal of anatomy · 2019Article
- Genetic dissection of anterior segment dysgenesis caused by aDisease models & mechanisms · 2017Article
- Smoothened is a poor prognosis factor and a potential therapeutic target in glioma.Scientific reports · 2017Article
- Non-essential role for cilia in coordinating precise alignment of lens fibres.Mechanisms of development · 2016Article
- Presenilin gene function and Notch signaling feedback regulation in the developing mouse lens.Differentiation; research in biological diversityArticle
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Various studies suggest that Hedgehog (Hh) signalling plays roles in human and zebrafish ocular development. Recent studies (Kerr et al., Invest Ophthalmol Vis Sci. 2012; 53, 3316-30) showed that conditionally activating Hh signals promotes murine lens epithelial cell proliferation and disrupts fibre differentiation. In this study we examined the expression of the Hh pathway and the requirement for the Smoothened gene in murine lens development. Expression of Hh pathway components in developing lens was examined by RT-PCR, immunofluorescence and in situ hybridisation. The requirement of Smo in lens development was determined by conditional loss-of-function mutations, using LeCre and MLR10 Cre transgenic mice. The phenotype of mutant mice was examined by immunofluorescence for various markers of cell cycle, lens and cornea differentiation. Hh pathway components (Ptch1, Smo, Gli2, Gli3) were detected in lens epithelium from E12.5. Gli2 was particularly localised to mitotic nuclei and, at E13.5, Gli3 exhibited a shift from cytosol to nucleus, suggesting distinct roles for these transcription factors. Conditional deletion of Smo, from ∼E12.5 (MLR10 Cre) did not affect ocular development, whereas deletion from ∼E9.5 (LeCre) resulted in lens and corneal defects from E14.5. Mutant lenses were smaller and showed normal expression of p57Kip2, c-Maf, E-cadherin and Pax6, reduced expression of FoxE3 and Ptch1 and decreased nuclear Hes1. There was normal G1-S phase but decreased G2-M phase transition at E16.5 and epithelial cell death from E14.5-E16.5. Mutant corneas were thicker due to aberrant migration of Nrp2+ cells from the extraocular mesenchyme, resulting in delayed corneal endothelial but normal epithelial differentiation. These results indicate the Hh pathway is required during a discrete period (E9.5-E12.5) in lens development to regulate lens epithelial cell proliferation, survival and FoxE3 expression. Defective corneal development occurs secondary to defects in lens and appears to be due to defective migration of peri-ocular Nrp2+ neural crest/mesenchymal cells.
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