Disruption of eyelid and cornea morphogenesis by epithelial β-catenin gain-of-function.
OBJECTIVE
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.
Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan.
Shin
S
Mizoguchi
Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan.
Kentaro
K
Suzuki
Department of Ophthalmology, University of Cincinnati School of Medicine, Cincinnati, Ohio.
Jianhua
J
Zhang
Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan.
Osamu
O
Yamanaka
Department of Ophthalmology, University of Cincinnati School of Medicine, Cincinnati, Ohio.
Chia-Yang
CY
Liu
Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan.
Yuka
Y
Okada
Laboratory Animal Center, Wakayama Medical University, Wakayama, Japan.
Masayasu
M
Miyajima
Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan.
Masahide
M
Kokado
Department of Ophthalmology, University of Cincinnati School of Medicine, Cincinnati, Ohio.
Winston W Y
WW
Kao
Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan.
Gen
G
Yamada
Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan.
Shizuya
S
Saika
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D003315:Cornea / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D005143:Eyelids / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D053555:Keratin-5 / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics; D009154:Mutation; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism*
C495267:CTNNB1 protein, mouse; D053555:Keratin-5; D051176:beta Catenin