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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

Cell proliferation by the detection of incorporation of BrdU. At E15.5, quite a few cells in the epithelium (Epi) and stroma are labeled for bromo-deoxyuridine (BrdU) in the wild-type (WT) cornea (A), while incidence of BrdU-labeled cells is frequently observed in a mutant embryo (B). Frames C, D, E, and F indicate the boxed areas in Frames A and B, respectively. Bar, 100 μm (A, B), 10 μm (C–F).
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f7: Cell proliferation by the detection of incorporation of BrdU. At E15.5, quite a few cells in the epithelium (Epi) and stroma are labeled for bromo-deoxyuridine (BrdU) in the wild-type (WT) cornea (A), while incidence of BrdU-labeled cells is frequently observed in a mutant embryo (B). Frames C, D, E, and F indicate the boxed areas in Frames A and B, respectively. Bar, 100 μm (A, B), 10 μm (C–F).

Mentions: Impairment of intraepithelial differentiation from the basal layer toward the superficial layer might be associated with changes in cell proliferation, which can be examined with BrdU labeling. At E13.5, the incidence of BrdU-labeling in the embryonic corneal epithelium was similar between the WT and mutant embryos (Appendix 1, panel F,G). At E15.5, many epithelial cells were labeled with BrdU immunohistochemistry in the mutant corneal epithelium (Figure 7B,D), while such BrdU-labeled cells were less frequently observed in the WT corneal epithelium (Figure 7A,C).


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)

Cell proliferation by the detection of incorporation of BrdU. At E15.5, quite a few cells in the epithelium (Epi) and stroma are labeled for bromo-deoxyuridine (BrdU) in the wild-type (WT) cornea (A), while incidence of BrdU-labeled cells is frequently observed in a mutant embryo (B). Frames C, D, E, and F indicate the boxed areas in Frames A and B, respectively. Bar, 100 μm (A, B), 10 μm (C–F).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7: Cell proliferation by the detection of incorporation of BrdU. At E15.5, quite a few cells in the epithelium (Epi) and stroma are labeled for bromo-deoxyuridine (BrdU) in the wild-type (WT) cornea (A), while incidence of BrdU-labeled cells is frequently observed in a mutant embryo (B). Frames C, D, E, and F indicate the boxed areas in Frames A and B, respectively. Bar, 100 μm (A, B), 10 μm (C–F).
Mentions: Impairment of intraepithelial differentiation from the basal layer toward the superficial layer might be associated with changes in cell proliferation, which can be examined with BrdU labeling. At E13.5, the incidence of BrdU-labeling in the embryonic corneal epithelium was similar between the WT and mutant embryos (Appendix 1, panel F,G). At E15.5, many epithelial cells were labeled with BrdU immunohistochemistry in the mutant corneal epithelium (Figure 7B,D), while such BrdU-labeled cells were less frequently observed in the WT corneal epithelium (Figure 7A,C).

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