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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 intermediate filament components in the corneal epithelium at E17.5. The wild-type (WT) corneal epithelium (A, Epi) is labeled for keratin 12, while keratin 12 is not detected in the mutant corneal epithelium (B, Epi). Stroma, corneal stroma; Bar, 50 μm.
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f6: Expression pattern of intermediate filament components in the corneal epithelium at E17.5. The wild-type (WT) corneal epithelium (A, Epi) is labeled for keratin 12, while keratin 12 is not detected in the mutant corneal epithelium (B, Epi). Stroma, corneal stroma; Bar, 50 μm.

Mentions: Because the β-catenin signal is closely related to cell differentiation and cell phenotype control, the epithelial–mesenchymal transition (EMT), we examined whether gof-β-catenin affected differentiation of the corneal epithelium by using immunohistochemical analysis of intermediate filament components. We first examined the characteristics of epithelial differentiation by examining the expression pattern of keratin 12, the marker of cornea-type epithelium differentiation, and keratin 14. In WT embryos, the keratin 12 protein was negative in the cornea at E13.5 (Appendix 1, panel A), and expression in the corneal epithelium was detected at E15.5 (Appendix 1, panel B); marked expression was detected at E17.5 (Figure 6A). However, the keratin 12 protein was not detected in the corneal epithelium throughout E13.5–17.5 (Figure 6B). Keratin 14 was observed in the basal cells of the WT corneal epithelium (Appendix 1, panel C). Keratin 14 was markedly expressed in epithelial nodules (Appendix 1, panel D). Focal hyperproliferation of the conjunctival epithelium was also observed in the mutant embryos (Appendix 1, panel E).


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 intermediate filament components in the corneal epithelium at E17.5. The wild-type (WT) corneal epithelium (A, Epi) is labeled for keratin 12, while keratin 12 is not detected in the mutant corneal epithelium (B, Epi). Stroma, corneal stroma; Bar, 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Expression pattern of intermediate filament components in the corneal epithelium at E17.5. The wild-type (WT) corneal epithelium (A, Epi) is labeled for keratin 12, while keratin 12 is not detected in the mutant corneal epithelium (B, Epi). Stroma, corneal stroma; Bar, 50 μm.
Mentions: Because the β-catenin signal is closely related to cell differentiation and cell phenotype control, the epithelial–mesenchymal transition (EMT), we examined whether gof-β-catenin affected differentiation of the corneal epithelium by using immunohistochemical analysis of intermediate filament components. We first examined the characteristics of epithelial differentiation by examining the expression pattern of keratin 12, the marker of cornea-type epithelium differentiation, and keratin 14. In WT embryos, the keratin 12 protein was negative in the cornea at E13.5 (Appendix 1, panel A), and expression in the corneal epithelium was detected at E15.5 (Appendix 1, panel B); marked expression was detected at E17.5 (Figure 6A). However, the keratin 12 protein was not detected in the corneal epithelium throughout E13.5–17.5 (Figure 6B). Keratin 14 was observed in the basal cells of the WT corneal epithelium (Appendix 1, panel C). Keratin 14 was markedly expressed in epithelial nodules (Appendix 1, panel D). Focal hyperproliferation of the conjunctival epithelium was also observed in the mutant embryos (Appendix 1, panel E).

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