title: Molecular description of eye defects in the zebrafish Pax6b mutant, sunrise, reveals a Pax6b-dependent genetic network in the developing anterior chamber.
abstract: 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.
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, Germany.
authors.forename: Masanari
authors.initials: M
authors.lastname: Takamiya
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, Germany.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Weger
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Schindler
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Beil
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, Germany.
authors.forename: Lixin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, Germany.
authors.forename: Olivier
authors.initials: O
authors.lastname: Armant
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Ferg
authors.affiliation: Eye Center, Freiburg University Medical Center, Killianstr. 5, 79106 Freiburg, Germany.
authors.forename: Günther
authors.initials: G
authors.lastname: Schlunck
authors.affiliation: Eye Center, Freiburg University Medical Center, Killianstr. 5, 79106 Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reinhard
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dickmeis
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, Germany.
authors.forename: Sepand
authors.initials: S
authors.lastname: Rastegar
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Postfach 3640, 76021 Karlsruhe, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Strähle
mesh_terms: D000818:Animals; D000867:Anterior Chamber / Q000254:growth & development* / Q000378:metabolism* / Q000473:pathology; D004728:Endothelium, Corneal / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000254:growth & development; D009154:Mutation; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012160:Retina / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development*
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins