Molecular Description of Eye Defects in the Zebrafish Pax6b Mutant, sunrise, Reveals a Pax6b-Dependent Genetic Network in the Developing Anterior Chamber

Takamiya, M., Weger, B.D., Schindler, S., Beil, T., Yang, L., Armant, O., Ferg, M., Schlunck, G., Reinhard, T., Dickmeis, T., Rastegar, S., Strähle, U.
PLoS One   10: e0117645 (Journal)
Registered Authors
Armant, Olivier, Beil, Tanja, Dickmeis, Thomas, Ferg, Marco, Rastegar, Sepand, Schindler, Simone, Strähle, Uwe, Takamiya, Masanari, Weger, Benjamin, Yang, Lixin
GEO:GSE24595, GEO:GSE24599, GEO:GSE24593
MeSH Terms
  • Animals
  • Anterior Chamber/growth & development*
  • Anterior Chamber/metabolism*
  • Anterior Chamber/pathology
  • Endothelium, Corneal/growth & development
  • Endothelium, Corneal/metabolism
  • Endothelium, Corneal/pathology
  • Eye Proteins/genetics*
  • Eye Proteins/metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Gene Regulatory Networks*
  • Homeodomain Proteins/genetics*
  • Homeodomain Proteins/metabolism
  • Larva/genetics
  • Larva/growth & development
  • Mutation*
  • Paired Box Transcription Factors/genetics*
  • Paired Box Transcription Factors/metabolism
  • Repressor Proteins/genetics*
  • Repressor Proteins/metabolism
  • Retina/growth & development
  • Retina/metabolism
  • Retina/pathology
  • Zebrafish/genetics*
  • Zebrafish/growth & development*
25692557 Full text @ PLoS One
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.
Genes / Markers
Show all Figures
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes