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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

HE histology of eyes of a WT embryo and a mutant embryo with gof-β-catenin in epithelial tissues. Hematoxylin and eosin (HE) histology shows a clear difference in the cellular architecture of the eyelid anlage and the cornea between the wild-type (WT) embryo and the mutant embryo with gain-of-function (gof)-β-catenin. No obvious difference in the structure of the eye and eyelids between the WT (A) and mutant embryos (B) was observed at E13.5. At E15.5, the eyelid (arrows) development is impaired (D) compared with the WT tissue (C). At E17.5 and E18.5, the cornea is completely covered with fused eyelids (arrows) in the WT embryo (E, G), while no eyelids, but just anlage (arrow) of an eyelid, are observed in the mutant (F, H). The surface of the cornea is thicker with an irregular surface in the mutant eye while smooth curvature is seen in the WT embryo (compare H to G). Bar, 100 μm.
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f2: HE histology of eyes of a WT embryo and a mutant embryo with gof-β-catenin in epithelial tissues. Hematoxylin and eosin (HE) histology shows a clear difference in the cellular architecture of the eyelid anlage and the cornea between the wild-type (WT) embryo and the mutant embryo with gain-of-function (gof)-β-catenin. No obvious difference in the structure of the eye and eyelids between the WT (A) and mutant embryos (B) was observed at E13.5. At E15.5, the eyelid (arrows) development is impaired (D) compared with the WT tissue (C). At E17.5 and E18.5, the cornea is completely covered with fused eyelids (arrows) in the WT embryo (E, G), while no eyelids, but just anlage (arrow) of an eyelid, are observed in the mutant (F, H). The surface of the cornea is thicker with an irregular surface in the mutant eye while smooth curvature is seen in the WT embryo (compare H to G). Bar, 100 μm.

Mentions: HE histology of the eyelid anlage seemed to be similar between the WT and mutant embryos at E13.5 (Figure 2A,B). However, the mesenchymal cells in the periocular tissue of the mutant embryo (Figure 2B) seemed to be more densely packed compared with the WT littermate at this embryonic stage (Figure 2A). Morphogenesis of the upper and lower eyelids was severely impaired in the mutant embryo of gof-β-catenin at E15.5 (Figure 2D) compared with the WT embryo (Figure 2C). At E17.5 and E18.5, eyelid fusion can be readily seen in the wild-type embryo (Figure 2E,G), while in the mutant the cornea is not covered by fused eyelids (Figure 2F,H) with an uneven corneal epithelium (described in detail below). Higher magnification observation showed that the mesenchymal cells in the periocular tissue of a mutant embryo (Figure 2H) still seemed to be more densely packed compared with the WT littermate (Figure 2G) at E18.5 similar to embryos at earlier embryonic day points.


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)

HE histology of eyes of a WT embryo and a mutant embryo with gof-β-catenin in epithelial tissues. Hematoxylin and eosin (HE) histology shows a clear difference in the cellular architecture of the eyelid anlage and the cornea between the wild-type (WT) embryo and the mutant embryo with gain-of-function (gof)-β-catenin. No obvious difference in the structure of the eye and eyelids between the WT (A) and mutant embryos (B) was observed at E13.5. At E15.5, the eyelid (arrows) development is impaired (D) compared with the WT tissue (C). At E17.5 and E18.5, the cornea is completely covered with fused eyelids (arrows) in the WT embryo (E, G), while no eyelids, but just anlage (arrow) of an eyelid, are observed in the mutant (F, H). The surface of the cornea is thicker with an irregular surface in the mutant eye while smooth curvature is seen in the WT embryo (compare H to G). Bar, 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: HE histology of eyes of a WT embryo and a mutant embryo with gof-β-catenin in epithelial tissues. Hematoxylin and eosin (HE) histology shows a clear difference in the cellular architecture of the eyelid anlage and the cornea between the wild-type (WT) embryo and the mutant embryo with gain-of-function (gof)-β-catenin. No obvious difference in the structure of the eye and eyelids between the WT (A) and mutant embryos (B) was observed at E13.5. At E15.5, the eyelid (arrows) development is impaired (D) compared with the WT tissue (C). At E17.5 and E18.5, the cornea is completely covered with fused eyelids (arrows) in the WT embryo (E, G), while no eyelids, but just anlage (arrow) of an eyelid, are observed in the mutant (F, H). The surface of the cornea is thicker with an irregular surface in the mutant eye while smooth curvature is seen in the WT embryo (compare H to G). Bar, 100 μm.
Mentions: HE histology of the eyelid anlage seemed to be similar between the WT and mutant embryos at E13.5 (Figure 2A,B). However, the mesenchymal cells in the periocular tissue of the mutant embryo (Figure 2B) seemed to be more densely packed compared with the WT littermate at this embryonic stage (Figure 2A). Morphogenesis of the upper and lower eyelids was severely impaired in the mutant embryo of gof-β-catenin at E15.5 (Figure 2D) compared with the WT embryo (Figure 2C). At E17.5 and E18.5, eyelid fusion can be readily seen in the wild-type embryo (Figure 2E,G), while in the mutant the cornea is not covered by fused eyelids (Figure 2F,H) with an uneven corneal epithelium (described in detail below). Higher magnification observation showed that the mesenchymal cells in the periocular tissue of a mutant embryo (Figure 2H) still seemed to be more densely packed compared with the WT littermate (Figure 2G) at E18.5 similar to embryos at earlier embryonic day points.

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