PAX6 dosage effects on comeal development, growth, and wound healing

Natalie Dora, Jingxing Ou, Romana Kucerova, Ida Parisi, John D. West, J. Martin Collinson

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The requirement for correct dosage of the transcription factor Pax6 during corneal growth and development was investigated using the Pax6-overexpressing (PAX77) transgenic mouse. Transgenics had a microcornea phenotype due to failure of postnatal growth, associated with reduction in the number of cells layers in the corneal epithelium. Cell cycle progression was monitored using bromodeoxyuridine, p63, cyclin E, and phosphohistone-3 labeling: proliferation rates were higher in PAX77(+) than wild-type, without a concomitant increase in apoptosis. Hence, failure of proliferation did not underlie microcornea. PAX77(+) corneal epithelia had reduced levels of cytokeratin-12, and exhibited severe wound healing delay that, in contrast to Pax6(+/-) mice, could not be modulated by exogenous growth factors. PAX77(+) lenses showed partial failure of lens fiber differentiation. The data demonstrate that anterior eye development is very sensitive to Pax6 dosage. Although there are similarities between the eye phenotype of Pax6 heterozygotes and overexpressing mice, there are also striking differences.

Original languageEnglish
Pages (from-to)1295-1306
Number of pages12
JournalDevelopmental Dynamics
Volume237
Issue number5
Early online date3 Apr 2008
DOIs
Publication statusPublished - May 2008

Keywords

  • cornea
  • Pax6
  • gene dosage
  • anterior segment
  • wound healing
  • aniridia-related keratopathy
  • PAX6(+/-) ,ouse model
  • metalloproteinase gelatinase B
  • corneal epithelial-cells
  • homeobox-containing gene
  • intraocular-pressure
  • stem-cells
  • chick eye
  • segment abnormalities
  • lens development

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