Abstract
Purpose: :
The effects of introducing β-catenin gain-of-function mutation in the surface ectoderm of the cornea and eyelids were examined in the mice.
Methods: :
Cre-mediated systems in keratin 5 (K5)-expressing epithelial basal cells was employed to drive the expression of β-catenin gain-of-function. Triple-transgenic mice (K5-Cre-Catnb(ex3)fl/+BmprIAfl/+ or K5-Cre-Catnb(ex3)fl/+BmprIAfl/fl) were generated to examine the effects of β-catenin overexpression on morphogenesis of cornea and eyelids in the presence or absence of Bmp receptor rIA(Alk3). β-catenin with the mutation of a.a. for phophorylation in exon 3 is resistant to degradation mimicing β-catenin activation. Histology and expression pattern of β-catenin, K12, K14, collagen I and BrdU incorporation was examined at E15.5 (n = 4) and E17.5 (n = 3).
Results: :
Nodular hyperproliferation in the corneal epithelium and hypoplasia of the eyelids were observed with β-catenin gain-of-function in epithelial basal cells. Such phenotype was not rescued by introducing mutation of Bmp receptor rIA. The hyperplastic nodules in corneal epithelium and epidermis were labeled for β-catenin and BrdU. Expression of K12 was suppressed and that of K 14 was upregulated in mutant corneal epithelium. BrdU incorporation in keratocytes was found to be increased. Collagen I expression was severely downregulated in corneal stroma and eyelid epidermis.
Conclusions: :
Aberrant expression of β-catenin gain-of-function in surface ectoderm impairs eyelids morphogenesis and induces tumor-like hyperproliferation in corneal epithelium in a mouse embryo. Proliferation and maturation of underlying keratocytes was also affected.
Keywords: anterior segment • eyelid • cell adhesions/cell junctions