May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Co-Operative Roles for E and N-Cadherin During Vertebrate Lens Development
Author Affiliations & Notes
  • G. F. Pontoriero
    Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
  • A. N. Smith
    Divisions of Developmental Biology and Ophthalmology, Children’s Hospital Research Foundation, Cincinnati, Ohio
  • R. A. Lang
    Divisions of Developmental Biology and Ophthalmology, Children’s Hospital Research Foundation, Cincinnati, Ohio
  • J. A. West-Mays
    Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
  • Footnotes
    Commercial Relationships  G.F. Pontoriero, None; A.N. Smith, None; R.A. Lang, None; J.A. West-Mays, None.
  • Footnotes
    Support  NIH EY11910 (JWM)
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5407. doi:
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      G. F. Pontoriero, A. N. Smith, R. A. Lang, J. A. West-Mays; Co-Operative Roles for E and N-Cadherin During Vertebrate Lens Development. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5407.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Cell adhesion molecules are thought to play important roles in multiple aspects of lens development. Three cadherin molecules (E, N, and P) are expressed during embryonic lens development, but only E and N-cadherin are maintained in lens throughout the life of the lens. E-cadherin exhibits a lens epithelial cell-specific expression pattern, while N-cadherin is more broadly localized to both the epithelial and fibre cell compartments. Conditional deletion of either E or N-cadherin within the developing lens yields strikingly similar phenotypes and would suggest theses molecules possess redundant roles during lens development.

Methods: : To critically analyze the co-requirement of E-cadherin and N-cadherin in lens morphogenesis, a mouse lacking both of these cadherin molecules within the developing lens and surface ectoderm was created using the Cre-loxP approach. Resultant mutant progeny (Le-Cre+;Cdh1KO/flox;Cdh2flox/flox) were compared with wildtype littermates in order to detect any significant morphological or immunohistochemical differences.

Results: : At P7, Le-Cre+;Cdh1KO/flox;Cdh2flox/flox double conditional knockout mice exhibited microphthalmia, and only remnants of lens material. The iris had also fused with the overlying cornea, which in turn lacked a distinct corneal epithelium and endothelium. Le-Cre+;Cdh1KO/flox;Cdh2flox/flox mutants also possessed a fully laminated retina that appeared overgrown and grossly misfolded. At early embryonic timepoints, Le-Cre+;Cdh1KO/flox; Cdh2flox/flox mice developed a lens placode that invaginated to form a lens vesicle. However, the lumen of this vesicle was composed of a number of cells that were immunoreactive to Pax6 and also TUNEL positive. While the primary fibre cells continued to develop as embryogenesis progressed in the double conditional mutants, a distinct lens epithelial layer failed to develop (Pax6 negative) at E15.5 and onward. Comparisons with littermates lacking various combinations of E and N-cadherin, also suggest that the dosage of cadherin molecules present within the lens epithelium is critical for proper development of the lens.

Conclusions: : Progressive loss of the lens epithelial cell layer in the double Le-Cre+;Cdh1KO/flox;Cdh2flox/flox mutants indicates that E and N-cadherin have redundant roles in the development and maintenance of the lens epithelium.

Keywords: cell adhesions/cell junctions • development • genetics 
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