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PAX6 dosage effects on corneal development, growth, and wound healing
Author(s) -
Dorà Natalie,
Ou Jingxing,
Kucerova Romana,
Parisi Ida,
West John D.,
Collinson J. Martin
Publication year - 2008
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21528
Subject(s) - pax6 , biology , eye development , bromodeoxyuridine , wound healing , cornea , genetically modified mouse , cell growth , corneal epithelium , transgene , phenotype , microbiology and biotechnology , cancer research , endocrinology , immunology , transcription factor , genetics , gene , neuroscience
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. Developmental Dynamics 237:1295‐1306, 2008. © 2008 Wiley‐Liss, Inc.