PAX6 dosage effects on corneal development, growth, and wound healing.
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
Dorà
Natalie
N
School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, United Kingdom.
Ou
Jingxing
J
Kucerova
Romana
R
Parisi
Ida
I
West
John D
JD
Collinson
J Martin
JM
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation; D049109:Cell Proliferation; D003315:Cornea / Q000033:anatomy & histology / Q000473:pathology / Q000502:physiology; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D004848:Epithelium / Q000033:anatomy & histology / Q000502:physiology; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D018628:Gene Dosage; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007908:Lens, Crystalline / Q000473:pathology / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D019927:Cyclin E; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D010750:Phosphoproteins; D012097:Repressor Proteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse