ArticleInvestigative ophthalmology & visual science2012
A zebrafish model of axenfeld-rieger syndrome reveals that pitx2 regulation by retinoic acid is essential for ocular and craniofacial development.
Article in Investigative ophthalmology & visual science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed, 67 citations in OpenAlex.
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- Rewiring of the epigenome and chromatin architecture by exogenously induced retinoic acid signaling during zebrafish embryonic development.Nucleic acids research · 2024Article
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- Ophthalmological Manifestations of Axenfeld-Rieger Syndrome: Current Perspectives.Clinical ophthalmology (Auckland, N.Z.) · 2023Review
- Effect of Polydeoxyribonucleotide (PDRN) Treatment on Corneal Wound Healing in Zebrafish (International journal of molecular sciences · 2022Article
- TWIST1, a gene associated with Saethre-Chotzen syndrome, regulates extraocular muscle organization in mouse.Developmental biology · 2022Article
- Zebrafish Model of Stickler Syndrome Suggests a Role for Col2a1a in the Neural Crest during Early Eye Development.Journal of developmental biology · 2022Article
- Branchiomeric Muscle Development Requires Proper Retinoic Acid Signaling.Frontiers in cell and developmental biology · 2021Article
- Genetics Underlying the Interactions between Neural Crest Cells and Eye Development.Journal of developmental biology · 2020Review
- Local retinoic acid signaling directs emergence of the extraocular muscle functional unit.PLoS biology · 2020Article
- Optic cup morphogenesis requires neural crest-mediated basement membrane assembly.Development (Cambridge, England) · 2020Article
- The Ocular Neural Crest: Specification, Migration, and Then What?Frontiers in cell and developmental biology · 2020Review
- Spatiotemporal Characterization of Anterior Segment Mesenchyme Heterogeneity During Zebrafish Ocular Anterior Segment Development.Frontiers in cell and developmental biology · 2020Article
- Genetics and functions of the retinoic acid pathway, with special emphasis on the eye.Human genomics · 2019Review
- Retinoic acid signaling pathways.Development (Cambridge, England) · 2019Review
- Transformation of the Transcriptomic Profile of Mouse Periocular Mesenchyme During Formation of the Embryonic Cornea.Investigative ophthalmology & visual science · 2019Article
- Retinoic acid signaling and neurogenic niche regulation in the developing peripheral nervous system of the cephalochordate amphioxus.Cellular and molecular life sciences : CMLS · 2018Article
- Article
- Retinoic Acid Maintains Function of Neural Crest-Derived Ocular and Craniofacial Structures in Adult Zebrafish.Investigative ophthalmology & visual science · 2018Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe homeobox transcription factor PITX2 is a known regulator of mammalian ocular development, and human PITX2 mutations are associated with Axenfeld-Rieger syndrome (ARS). However, the treatment of patients with ARS remains mostly supportive and palliative.
methodsThe authors used molecular genetic, pharmacologic, and embryologic techniques to study the biology of ARS in a zebrafish model that uses transgenes to mark neural crest and muscle cells in the head.
resultsThe authors demonstrated in vivo that pitx2 is a key downstream target of retinoic acid (RA) in craniofacial development, and this pathway is required for coordinating neural crest, mesoderm, and ocular development. pitx2a knockdown using morpholino oligonucleotides disrupts jaw and pharyngeal arch formation and recapitulates ocular characteristics of ARS, including corneal and iris stroma maldevelopment. These phenotypes could be rescued with human PITX2A mRNA, demonstrating the specificity of the knockdown and evolutionary conservation of pitx2a function. Expression of the ARS dominant negative human PITX2A K50E allele also caused ARS-like phenotypes. Similarly, inhibition of RA synthesis in the developing eye (genetic or pharmacologic) disrupted craniofacial and ocular development, and human PITX2A mRNA partially rescued these defects.
conclusionsRA regulation of pitx2 is essential for coordinating interactions among neural crest, mesoderm, and developing eye. The marked evolutionary conservation of Pitx2 function in eye and craniofacial development makes zebrafish a potentially powerful model of ARS, amenable to in vivo experimentation and development of potential therapies.
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