Molecular description of eye defects in the zebrafish Pax6b mutant, sunrise, reveals a Pax6b-dependent genetic network in the developing anterior chamber
| Autor: | Takamiya, Masanari, Weger, Benjamin D., Schindler, Simone, Beil, Tanja, Yang, Lixin, Armant, Olivier, Ferg, Marco, Schlunck, Günther, Reinhard, Thomas, Dickmeis, Thomas, Rastegar, Sepand, Strähle, Uwe |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Homeodomain Proteins
PAX6 Transcription Factor genetic structures Anterior Chamber Gene Expression Profiling Science Endothelium Corneal Gene Expression Regulation Developmental Retina eye diseases Repressor Proteins Larva Mutation Animals Paired Box Transcription Factors Medicine Gene Regulatory Networks sense organs Eye Proteins Zebrafish Research Article |
| Zdroj: | PLoS ONE, Vol 10, Iss 2, p e0117645 (2015) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | The cornea is a central component of the camera eye of vertebrates and even slight corneal disturbances severely affect vision. The transcription factor PAX6 is required for normal eye development, namely the proper separation of the lens from the developing cornea and the formation of the iris and anterior chamber. Human PAX6 mutations are associated with severe ocular disorders such as aniridia, Peters anomaly and chronic limbal stem cell insufficiency. To develop the zebrafish as a model for corneal disease, we first performed transcriptome and in situ expression analysis to identify marker genes to characterise the cornea in normal and pathological conditions. We show that, at 7 days post fertilisation (dpf), the zebrafish cornea expresses the majority of marker genes (67/84 tested genes) found also expressed in the cornea of juvenile and adult stages. We also characterised homozygous pax6b mutants. Mutant embryos have a thick cornea, iris hypoplasia, a shallow anterior chamber and a small lens. Ultrastructure analysis revealed a disrupted corneal endothelium. pax6b mutants show loss of corneal epithelial gene expression including regulatory genes (sox3, tfap2a, foxc1a and pitx2). In contrast, several genes (pitx2, ctnnb2, dcn and fabp7a) were ectopically expressed in the malformed corneal endothelium. Lack of pax6b function leads to severe disturbance of the corneal gene regulatory programme. |
| Databáze: | OpenAIRE |
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