Disruption of mouse corneal epithelial differentiation by conditional inactivation of pnn.
Purpose. To investigate the specific role of Pinin (Pnn) in the development of anterior eye segment in mice. Methods. Conditional inactivation of Pnn in the developing surface eye ectoderm and lens was achieved by creating mice carrying a Pnn null and a floxed Pnn allele as well as a Pax6-Cre-GFP (Le-Cre) transgene. The resultant Pnn conditional knockout mice were examined by histologic and immunohistologic approaches. Results. Pax6-Cre-mediated deletion of Pnn resulted in severe malformation of lens placode-derived tissues including cornea and lens. Pnn mutant corneal epithelium displayed the loss of corneal epithelial identity and appeared epidermis-like, downregulating corneal keratins (K12) and ectopically expressing epidermal keratins (K10 and K14). This squamous metaplasia of Pnn mutant corneal epithelium closely correlated with significantly elevated beta-catenin activity and Tcf4 level. In addition, Pnn inactivation also led to misregulated level of p68 RNA helicase in mutant corneal epithelium. Conclusions. These data indicate that Pnn plays an essential role in modulating and/or orchestrating the activities of major developmental factors of anterior eye segments.
Joo
Jeong-Hoon
JH
Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida, USA.
Kim
Yong H
YH
Dunn
Nicholas W
NW
Sugrue
Stephen P
SP
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics*; D016923:Cell Death; D002454:Cell Differentiation; D049109:Cell Proliferation; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D004268:DNA-Binding Proteins; D019573:Epithelium, Corneal / Q000378:metabolism / Q000473:pathology*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D020868:Gene Silencing / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D007633:Keratins / Q000378:metabolism; D008297:Male; D008679:Metaplasia / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000073940:Transcription Factor 4; D051176:beta Catenin / Q000378:metabolism
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C495267:CTNNB1 protein, mouse; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; C491175:Pnn protein, mouse; D012097:Repressor Proteins; C090743:Tcf4 protein, mouse; D000073940:Transcription Factor 4; D051176:beta Catenin; D049452:Green Fluorescent Proteins; D007633:Keratins; C045073:Cre recombinase; D019426:Integrases; D053487:DEAD-box RNA Helicases