title: Atypical Cadherin Fat1 Is Required for Lens Epithelial Cell Polarity and Proliferation but Not for Fiber Differentiation.
abstract: OBJECTIVE
  The Fat family of atypical cadherins, originally identified in Drosophila, play diverse roles during embryogenesis and adult tissue maintenance. Among four mammalian members, Fat1 is essential for kidney and muscle organization, and is also essential for eye development; Fat1 knockout causes partial penetrant microphthalmia or anophthalmia. To account for the partial penetrance of the Fat1 phenotype, involvement of Fat4 in eye development was assessed. Lens phenotypes in Fat1 and 4 knockouts were also examined.
  
  
  METHODS
  Fat1 and Fat4 mRNA expression was examined by in situ hybridization. Knockout phenotypes of Fat1 and Fat4 were analyzed by hematoxylin and eosin (H&E) and immunofluorescent staining.
  
  
  RESULTS
  We found Fat4 knockout did not affect eye induction or enhance severity of Fat1 eye defects. Although Fat1 and Fat4 mRNAs are similarly expressed in the lens epithelial cells, only Fat1 knockout caused a fully penetrant lens epithelial cell defect, which was apparent at embryonic day 14.5 (E14.5). The columnar structure of the lens epithelial cells was disrupted and in some regions cell aggregates were formed. In these multilayered regions, apical cell junctions were fragmented and the apical-basal polarity was lost. EdU incorporation assay also showed enhanced proliferation in the lens epithelial cells. Interestingly, these defects were found mainly in the central zone of the epithelial layer. The lens epithelial cells of the germinative zone maintained their normal morphology and fiber differentiation occurred normally at the equator.
  
  
  CONCLUSIONS
  These observations indicate that Fat1 is essential for lens epithelial cell polarity and proliferation but not for terminal differentiation.
authors.affiliation: Save Sight Institute University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sugiyama
authors.affiliation: Save Sight Institute University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shelley
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Badouel
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: McNeill
authors.affiliation: Save Sight Institute University of Sydney, Sydney, New South Wales, Australia.
authors.forename: John W
authors.initials: JW
authors.lastname: McAvoy
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000502:physiology*; D007365:Intercellular Junctions / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D015820:Cadherins; C506555:Fat4 protein, mouse; D012333:RNA, Messenger; C502406:fat1 protein, mouse