ArticleInvestigative ophthalmology & visual science2016
AP-2β Is a Downstream Effector of PITX2 Required to Specify Endothelium and Establish Angiogenic Privilege During Corneal Development.
Article in Investigative ophthalmology & visual science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Classifications of anterior segment structure of congenital corneal opacity in infants and toddlers by ultrasound biomicroscopy and slit-lamp microscopic photographs: an observational study.BMC ophthalmology · 2024Observational
- Comparison between Cultivated Oral Mucosa and Ocular Surface Epithelia for COMET Patients Follow-Up.International journal of molecular sciences · 2023Article
- Deletion of transcription factor AP-2β from the developing murine trabecular meshwork region leads to progressive glaucomatous changes.Journal of neuroscience research · 2022Article
- Single cell transcriptomics reveals the heterogeneity of the human cornea to identify novel markers of the limbus and stroma.Scientific reports · 2021Article
- Conditional Deletion of AP-2β in the Periocular Mesenchyme of Mice Alters Corneal Epithelial Cell Fate and Stratification.International journal of molecular sciences · 2021Article
- Corneal development: Role of the periocular mesenchyme and bi-directional signaling.Experimental eye research · 2020Review
- Genetics Underlying the Interactions between Neural Crest Cells and Eye Development.Journal of developmental biology · 2020Review
- AP-2β is required for formation of the murine trabecular meshwork and Schlemm's canal.Experimental eye research · 2020Article
- Generation and validation of a PITX2-EGFP reporter line of human induced pluripotent stem cells enables isolation of periocular mesenchymal cells.The Journal of biological chemistry · 2020Article
- Localization ofThe journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2019Article
- Application of corneal injury models in dual fluorescent reporter transgenic mice to understand the roles of the cornea and limbus in angiogenic and lymphangiogenic privilege.Scientific reports · 2019Article
- Transcription factor TFAP2B up-regulates human corneal endothelial cell-specific genes during corneal development and maintenance.The Journal of biological chemistry · 2019Article
- Transformation of the Transcriptomic Profile of Mouse Periocular Mesenchyme During Formation of the Embryonic Cornea.Investigative ophthalmology & visual science · 2019Article
- Computational approaches for predicting key transcription factors in targeted cell reprogramming (Review).Molecular medicine reports · 2018Review
- PITX2 deficiency and associated human disease: insights from the zebrafish model.Human molecular genetics · 2018Article
- AP-2β inhibits hepatocellular carcinoma invasion and metastasis through Slug and Snail to suppress epithelial-mesenchymal transition.Theranostics · 2018Article
- Restricted Presence of POU6F2 in Human Corneal Endothelial Cells Uncovered by Extension of the Promoter-level Expression Atlas.EBioMedicine · 2017Article
- Genetic dissection of anterior segment dysgenesis caused by aDisease models & mechanisms · 2017Article
- Foxc1 and Foxc2 in the Neural Crest Are Required for Ocular Anterior Segment Development.Investigative ophthalmology & visual science · 2017Article
- Conditional deletion of AP-2β in mouse cranial neural crest results in anterior segment dysgenesis and early-onset glaucoma.Disease models & mechanisms · 2016Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeThe homeodomain transcription factor, PITX2, is at the apex of a genetic pathway required for corneal development, but the critical effector genes regulated by the PITX2 remain unknown. The purpose of this study was to discover and validate PITX2-dependent mechanisms required for specifying cell lineages and establishing angiogenic privilege within the developing cornea.
methodsMicroarrays were used to compare gene expression in corneas isolated from temporal Pitx2 knockout embryos and control littermates. Quantitative RT-PCR and immunohistochemistry was used to further validate Tfap2b expression differences in Pitx2 knockout versus control corneas. In situ hybridization and protein immunohistochemistry were used to assay eyes of a Tfap2b allelic series of embryos to identify differentiated cellular lineages in the cornea, blood vessel endothelium, or lymphatic vessel endothelium.
resultsWe show that PITX2 is required for the expression of Tfap2b, encoding the AP-2β transcription factor, in the neural crest during corneal development. Markers of differentiated corneal epithelium and stroma are expressed in the absence of AP-2β. In contrast, markers of differentiated corneal endothelium are not expressed in the absence of AP-2β. Endomucin+ blood vessels are present throughout the developing corneal stroma in the absence of AP-2β, whereas LYVE1+ lymphatic vessels are not found.
conclusionsThe AP-2β transcription factor is an important effector of PITX2 function during corneal development, required for differentiation of corneal endothelium and establishment of angiogenic privilege. Unlike PITX2, AP-2β is not required for the early expression of available lineage specific markers for the corneal epithelium and stroma during embryogenesis, nor establishment of lymphangiogenic privilege. Therefore, additional PITX2-dependent factors likely regulate these latter processes during embryonic development. These results extend our understanding of the genetic mechanisms regulating cornea development.
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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 Socratic graph.