title: AP-2α is required after lens vesicle formation to maintain lens integrity.
abstract: BACKGROUND
  Transcription factors are critical in regulating lens development. The AP-2 family of transcription factors functions in differentiation, cell growth and apoptosis, and in lens and eye development. AP-2α, in particular, is important in early lens development, and when conditionally deleted at the placode stage defective separation of the lens vesicle from the surface ectoderm results. AP-2α's role during later stages of lens development is unknown. To address this, the MLR10-Cre transgene was used to delete AP-2α from the lens epithelium beginning at embryonic day (E) 10.5.
  
  
  RESULTS
  The loss of AP-2α after lens vesicle separation resulted in morphological defects beginning at E18.5. By P4, a small highly vacuolated lens with a multilayered epithelium was evident in the MLR10-AP-2α mutants. Epithelial cells appeared elongated and expressed fiber cell specific βB1 and γ-crystallins. Epithelial cell polarity and lens cell adhesion was disrupted and accompanied by the misexpression of ZO-1, N-Cadherin, and β-catenin. Cell death was observed in the mutant lens epithelium between postnatal day (P) 14 and P30, and correlated with altered arrangements of cells within the epithelium.
  
  
  CONCLUSIONS
  Our findings demonstrate that AP-2α continues to be required after lens vesicle separation to maintain a normal lens epithelial cell phenotype and overall lens integrity and to ensure correct fiber cell differentiation.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University Health Science Centre, Hamilton, Ontario, Canada.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Kerr
authors.forename: Mizna A
authors.initials: MA
authors.lastname: Zaveri
authors.forename: Michael L
authors.initials: ML
authors.lastname: Robinson
authors.forename: Trevor
authors.initials: T
authors.lastname: Williams
authors.forename: Judith A
authors.initials: JA
authors.lastname: West-Mays
mesh_terms: D000818:Animals; D002386:Cataract / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics; D004622:Embryo, Mammalian; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D004848:Epithelium / Q000378:metabolism / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D007908:Lens, Crystalline / Q000196:embryology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D050656:Transcription Factor AP-2 / Q000502:physiology*
chemical_list: D050656:Transcription Factor AP-2
keywords: AP-2; differentiation; lens development; lens epithelium; transcription factors
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