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Disruption of eyelid and cornea morphogenesis by epithelial β-catenin gain-of-function.

Mizoguchi S, Suzuki K, Zhang J, Yamanaka O, Liu CY, Okada Y, Miyajima M, Kokado M, Kao WW, Yamada G, Saika S - Mol. Vis. (2015)

Bottom Line: The ultrastructure of the ocular tissues of the E18.5 embryos was also examined.The mutant stroma exhibited impaired keratocyte differentiation with accelerated cell proliferation and reduction in the accumulation of collagen type I.The mutant embryos also showed hyperproliferative nodules in the ocular surface epithelia with anomaly of cornea-type epithelial differentiation and the absence of the epithelial basement membrane.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan.

ABSTRACT

Purpose: To examine the developmental pathobiology of the eyelid and the cornea caused by epithelial β-catenin gain-of-function (gof) during mouse embryogenesis.

Methods: Compound mutant mice (Ctnnb1(GOFOSE) , gof of β-catenin in the epidermis and the ocular surface epithelium) were generated by time-mating keratin 5-promoter-Cre recombinase (Krt5-Cre) and Ctnnb1(fE3/WT) (floxed exon 3 of Ctnnb1) mice. Eyes obtained from wild-type (WT) and mutant embryos at various gestation stages until E18.5 were examined with histology and immunohistochemistry. The ultrastructure of the ocular tissues of the E18.5 embryos was also examined.

Results: Expression of the gof-β-catenin mutant protein in the epidermis severely impaired eyelid morphogenesis at E15.5, E17.5, and E18.5. The mutant stroma exhibited impaired keratocyte differentiation with accelerated cell proliferation and reduction in the accumulation of collagen type I. The mutant embryos also showed hyperproliferative nodules in the ocular surface epithelia with anomaly of cornea-type epithelial differentiation and the absence of the epithelial basement membrane.

Conclusions: Expression of the gof-β-catenin mutant protein in basal epithelial cells disrupts eyelid and cornea morphogenesis during mouse embryonic development due to the perturbation of cell proliferation and differentiation of the epithelium and the neural crest-derived mesenchyme.

No MeSH data available.


Related in: MedlinePlus

Expression pattern of keratocan and collagen type I in embryonic corneal stroma at E17.5. Stroma of the wild-type (WT) cornea is labeled for keratocan (A), while keratocan is not detected in the mutant corneal stroma (B). The entire corneal stroma of the WT embryo is positive for collagen type I (C). The mutant stroma lacks collagen I (D). Epi, corneal epithelium; Bar, 100 μm.
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f9: Expression pattern of keratocan and collagen type I in embryonic corneal stroma at E17.5. Stroma of the wild-type (WT) cornea is labeled for keratocan (A), while keratocan is not detected in the mutant corneal stroma (B). The entire corneal stroma of the WT embryo is positive for collagen type I (C). The mutant stroma lacks collagen I (D). Epi, corneal epithelium; Bar, 100 μm.

Mentions: To characterize the level of differentiation or maturation of keratocytes and the nature of the extracellular matrix of the corneal stroma, we then performed immunohistochemistry for the extracellular matrix components. Expression of keratocan is a hallmark of keratocyte-type differentiation. At E13.5, the corneal stroma of the WT and mutant littermates was not labeled with anti-keratocan antibodies (Appendix 1, panel H,I). At E15.5 (Appendix , panel J) and E17.5, immunoreactivity for keratocan was detected in the stroma of the wild-type mouse (Figure 9A) but completely absent in the mutant stroma (Figure 9B). We then evaluated the maturation of the stromal extracellular matrix by examining the protein expression of collagen type I (the major collagen in the corneal stroma).


Disruption of eyelid and cornea morphogenesis by epithelial β-catenin gain-of-function.

Mizoguchi S, Suzuki K, Zhang J, Yamanaka O, Liu CY, Okada Y, Miyajima M, Kokado M, Kao WW, Yamada G, Saika S - Mol. Vis. (2015)

Expression pattern of keratocan and collagen type I in embryonic corneal stroma at E17.5. Stroma of the wild-type (WT) cornea is labeled for keratocan (A), while keratocan is not detected in the mutant corneal stroma (B). The entire corneal stroma of the WT embryo is positive for collagen type I (C). The mutant stroma lacks collagen I (D). Epi, corneal epithelium; Bar, 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4522241&req=5

f9: Expression pattern of keratocan and collagen type I in embryonic corneal stroma at E17.5. Stroma of the wild-type (WT) cornea is labeled for keratocan (A), while keratocan is not detected in the mutant corneal stroma (B). The entire corneal stroma of the WT embryo is positive for collagen type I (C). The mutant stroma lacks collagen I (D). Epi, corneal epithelium; Bar, 100 μm.
Mentions: To characterize the level of differentiation or maturation of keratocytes and the nature of the extracellular matrix of the corneal stroma, we then performed immunohistochemistry for the extracellular matrix components. Expression of keratocan is a hallmark of keratocyte-type differentiation. At E13.5, the corneal stroma of the WT and mutant littermates was not labeled with anti-keratocan antibodies (Appendix 1, panel H,I). At E15.5 (Appendix , panel J) and E17.5, immunoreactivity for keratocan was detected in the stroma of the wild-type mouse (Figure 9A) but completely absent in the mutant stroma (Figure 9B). We then evaluated the maturation of the stromal extracellular matrix by examining the protein expression of collagen type I (the major collagen in the corneal stroma).

Bottom Line: The ultrastructure of the ocular tissues of the E18.5 embryos was also examined.The mutant stroma exhibited impaired keratocyte differentiation with accelerated cell proliferation and reduction in the accumulation of collagen type I.The mutant embryos also showed hyperproliferative nodules in the ocular surface epithelia with anomaly of cornea-type epithelial differentiation and the absence of the epithelial basement membrane.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan.

ABSTRACT

Purpose: To examine the developmental pathobiology of the eyelid and the cornea caused by epithelial β-catenin gain-of-function (gof) during mouse embryogenesis.

Methods: Compound mutant mice (Ctnnb1(GOFOSE) , gof of β-catenin in the epidermis and the ocular surface epithelium) were generated by time-mating keratin 5-promoter-Cre recombinase (Krt5-Cre) and Ctnnb1(fE3/WT) (floxed exon 3 of Ctnnb1) mice. Eyes obtained from wild-type (WT) and mutant embryos at various gestation stages until E18.5 were examined with histology and immunohistochemistry. The ultrastructure of the ocular tissues of the E18.5 embryos was also examined.

Results: Expression of the gof-β-catenin mutant protein in the epidermis severely impaired eyelid morphogenesis at E15.5, E17.5, and E18.5. The mutant stroma exhibited impaired keratocyte differentiation with accelerated cell proliferation and reduction in the accumulation of collagen type I. The mutant embryos also showed hyperproliferative nodules in the ocular surface epithelia with anomaly of cornea-type epithelial differentiation and the absence of the epithelial basement membrane.

Conclusions: Expression of the gof-β-catenin mutant protein in basal epithelial cells disrupts eyelid and cornea morphogenesis during mouse embryonic development due to the perturbation of cell proliferation and differentiation of the epithelium and the neural crest-derived mesenchyme.

No MeSH data available.


Related in: MedlinePlus