Essential role for Pbx1 in corneal morphogenesis.
OBJECTIVE
The Pbx TALE (three-amino-acid loop extension) homeodomain proteins interact with class 1 Hox proteins, which are master regulators of cell fate decisions. This study was performed to elucidate the role of the Pbx1 TALE protein in the corneal epithelium of mice.


METHODS
Pbx1(f/f) mice were crossed with mice containing Cre recombinase under the control of the K14 promoter. Subsequently, the eyes of these mice were dissected and prepared for histologic or molecular analysis.


RESULTS
Tissue-specific deletion of Pbx1 in the corneal epithelium of mice resulted in corneal dystrophy and clouding that was apparent in newborns and progressively worsened with age. Thickening of the cornea epithelium was accompanied by stromal infiltration with atypical basal cells, severe disorganization of stromal collagen matrix, and loss of corneal barrier function. High epithelial cell turnover was associated with perturbed expression of developmental regulators and aberrant differentiation, suggesting an important function for Pbx1 in determining corneal identity.


CONCLUSIONS
These studies establish an essential role of the Pbx1 proto-oncogene in corneal morphogenesis.
Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
Mark J
MJ
Murphy
Bozena K
BK
Polok
Daniel F
DF
Schorderet
Michael L
ML
Cleary
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D003315:Cornea / Q000254:growth & development*; D003318:Corneal Opacity / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D003319:Corneal Stroma / Q000378:metabolism / Q000473:pathology; D019573:Epithelium, Corneal / Q000378:metabolism / Q000473:pathology; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D005838:Genotype; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D019426:Integrases / Q000502:physiology; D007633:Keratins / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000502:physiology*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D012097:Repressor Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000502:physiology*
D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; C481797:Pbx1 protein, mouse; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D012097:Repressor Proteins; D014157:Transcription Factors; D007633:Keratins; C045073:Cre recombinase; D019426:Integrases; D001973:Bromodeoxyuridine