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Jie Huang, Ying Liu, David Beebe; Canonical Wnt signaling is required for lacrimal gland formation, eyelid closure and to suppress corneal cell fate in mouse conjunctival and eyelid epithelium. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5938.
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© ARVO (1962-2015); The Authors (2016-present)
Wnt signaling must be suppressed for the corneal epithelium to differentiate. Failure to inhibit Wnt signaling in Dkk2 knockout mice caused the corneal epithelium became epidermis (Mukhopadhyay, et al. Development 2006). Wnt signaling has also been suggested to inhibit lacrimal gland formation (Dean, et al. Dev Biol 2005). To better understand the function of Wnt signaling in specifying ocular surface ectodermal derivatives, we examined the cell fate of the corneal, conjunctival and eyelid margin epithelia in mice deficient in canonical Wnt signaling.
Transgenic mice expressing Cre recombinase in the ocular surface epithelia (LeCre) were mated to mice carrying floxed alleles of the Wnt co-receptors, Lrp5 and Lrp6. Antibodies to Sox9 and Aquaporin1 and antisense probes for Otx1, Barx2, Keratin12 andKeratin4 were used for immunofluorescence staining and in situ hybridization.
Lrp5/6 conditional knockout mice lacked lacrimal glands and had open eyelids at birth. Sox9 expression, which we found was required for lacrimal gland formation (2013 ARVO abstract by Chen, Huang, Liu and Beebe), was decreased at E14.5 in Lrp5/6 conditional knockout mice. The conjunctival and eyelid margin epithelia of Lrp5/6 conditional knockout mice showed ectopic patches of Keratin12 expression, a marker of corneal epithelial differentiation. Aquaporin1, an early marker of the corneal stroma, was present beneath the corneal epithelium, but not beneath the ectopic, K12-positive cells.
Canonical Wnt signaling is required for lacrimal gland formation and eyelid closure. Loss of Wnt signaling caused the transdifferentiation of conjunctival and eyelid epithelium to corneal epithelium. Suppressing Wnt signaling may assist in producing corneal epithelium from stem cells.
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