Limits...
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

Immunohistochemistry for laminin in the E18.5 corneal epithelium and its ultrastructural histology. Immunohistochemistry detects laminin in the epithelial basement membrane of the corneal epithelium (arrowheads) in the E18.5 wild-type (WT) embryo (A), while the epithelial nodules that grows downward to the stroma lacks a laminin-basement membrane (arrows; B). Ultrastructural observation shows that the corneal epithelium (C, Epi) forms stratification of the intraepithelial-differentiated cell in the WT tissue, while it consists of disarranged spheroidal epithelial epidermal cells (D, Epi) in the mutant tissue. Mutant epithelial cells in the mutant mouse lack upward differentiation. The epithelial–stromal interface is irregular in the mutant tissue with disorganized stromal connective tissue (Stroma) in the mutant cornea. Higher magnification observation shows that the WT corneal epithelium (Epi) has a basement membrane (arrows) between stroma (E), while the basal epithelial cells (Epi) lacks this structure at the interface with the underlying stroma in the mutant (F). Bar, 50 μm (A, B); 5 μm (C, D); 500 nm (E, F).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4522241&req=5

f5: Immunohistochemistry for laminin in the E18.5 corneal epithelium and its ultrastructural histology. Immunohistochemistry detects laminin in the epithelial basement membrane of the corneal epithelium (arrowheads) in the E18.5 wild-type (WT) embryo (A), while the epithelial nodules that grows downward to the stroma lacks a laminin-basement membrane (arrows; B). Ultrastructural observation shows that the corneal epithelium (C, Epi) forms stratification of the intraepithelial-differentiated cell in the WT tissue, while it consists of disarranged spheroidal epithelial epidermal cells (D, Epi) in the mutant tissue. Mutant epithelial cells in the mutant mouse lack upward differentiation. The epithelial–stromal interface is irregular in the mutant tissue with disorganized stromal connective tissue (Stroma) in the mutant cornea. Higher magnification observation shows that the WT corneal epithelium (Epi) has a basement membrane (arrows) between stroma (E), while the basal epithelial cells (Epi) lacks this structure at the interface with the underlying stroma in the mutant (F). Bar, 50 μm (A, B); 5 μm (C, D); 500 nm (E, F).

Mentions: Ultrastructural observation showed a regular arrangement of stratified epithelial cells on the surface of the WT cornea at E18.5 (Figure 5C). In the E18.5 mutant embryos, the superficial epithelial cells of the corneal epithelium failed to assume the flattened characteristic shape of the stratified superficial epithelium seen in the WT cornea (compare Figure 5D to Figure 5C). The E18.5 mutant epithelium lacked a subepithelial basement membrane at the interface with the underlying stroma (Figure 5F), while the WT epithelium had an obvious basement membrane structure (arrows, Figure 5E).


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)

Immunohistochemistry for laminin in the E18.5 corneal epithelium and its ultrastructural histology. Immunohistochemistry detects laminin in the epithelial basement membrane of the corneal epithelium (arrowheads) in the E18.5 wild-type (WT) embryo (A), while the epithelial nodules that grows downward to the stroma lacks a laminin-basement membrane (arrows; B). Ultrastructural observation shows that the corneal epithelium (C, Epi) forms stratification of the intraepithelial-differentiated cell in the WT tissue, while it consists of disarranged spheroidal epithelial epidermal cells (D, Epi) in the mutant tissue. Mutant epithelial cells in the mutant mouse lack upward differentiation. The epithelial–stromal interface is irregular in the mutant tissue with disorganized stromal connective tissue (Stroma) in the mutant cornea. Higher magnification observation shows that the WT corneal epithelium (Epi) has a basement membrane (arrows) between stroma (E), while the basal epithelial cells (Epi) lacks this structure at the interface with the underlying stroma in the mutant (F). Bar, 50 μm (A, B); 5 μm (C, D); 500 nm (E, F).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: Immunohistochemistry for laminin in the E18.5 corneal epithelium and its ultrastructural histology. Immunohistochemistry detects laminin in the epithelial basement membrane of the corneal epithelium (arrowheads) in the E18.5 wild-type (WT) embryo (A), while the epithelial nodules that grows downward to the stroma lacks a laminin-basement membrane (arrows; B). Ultrastructural observation shows that the corneal epithelium (C, Epi) forms stratification of the intraepithelial-differentiated cell in the WT tissue, while it consists of disarranged spheroidal epithelial epidermal cells (D, Epi) in the mutant tissue. Mutant epithelial cells in the mutant mouse lack upward differentiation. The epithelial–stromal interface is irregular in the mutant tissue with disorganized stromal connective tissue (Stroma) in the mutant cornea. Higher magnification observation shows that the WT corneal epithelium (Epi) has a basement membrane (arrows) between stroma (E), while the basal epithelial cells (Epi) lacks this structure at the interface with the underlying stroma in the mutant (F). Bar, 50 μm (A, B); 5 μm (C, D); 500 nm (E, F).
Mentions: Ultrastructural observation showed a regular arrangement of stratified epithelial cells on the surface of the WT cornea at E18.5 (Figure 5C). In the E18.5 mutant embryos, the superficial epithelial cells of the corneal epithelium failed to assume the flattened characteristic shape of the stratified superficial epithelium seen in the WT cornea (compare Figure 5D to Figure 5C). The E18.5 mutant epithelium lacked a subepithelial basement membrane at the interface with the underlying stroma (Figure 5F), while the WT epithelium had an obvious basement membrane structure (arrows, Figure 5E).

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