Purchase this article with an account.
Maureen Mongan, Qinghang Meng, Winston Kao, Ying Xia; The Developmental Roles of c-Jun in Ocular Surface Epithelium. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3064.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
At embryonic day (E) 15.5, the mouse eyelid closes as the result of eyelid epithelial cell migration. The MAP3K1-JNK signaling cascade is required for embryonic eyelid closure, but its downstream effectors have not been identified. c-Jun is a transcription factor and potential substrate of JNK. Here we used genetic tools to investigate the roles of c-Jun in ocular surface epithelium and its crosstalk with MAP3K1 in embryonic eyelid closure
The c-Junflox mice were used to cross with the lens epithelium (le)-cre mice to generate the c-JunΔOSE/ΔOSE mice, in which c-Jun was ablated specifically in the ocular surface epithelium. The Map3k1ΔKD/ΔKD mice express a kinase-dead MAP3K1 protein fused to a β-Galactosidase. Standard crossing techniques were used to generate the Map3k1+/ΔKDc-Jun+/ΔOSE double hemizygous mice. Fetuses were collected at E15.5-18.5 and postnatal day 1. The eyelid closure status was documented, eye morphology was examined by H&E, and the expression of c-Jun was detected by immunohistochemistry.
In the wild type E15.5 fetuses, strong c-Jun expression was found in the equatorial zone of the lens and the leading edge eyelid epithelium, weaker expression was detected in cornea and inner eyelid epithelium, but almost no expression was seen in the outer eyelid and skin epithelium. Besides the ocular surface epithelium, c-Jun was strongly expressed within the dermis of the eyelid, extra ocular muscles, brain and retina. In the c-JunΔOSE/ΔOSE fetuses, though c-Jun expression in other tissues remained strong, its expression in ocular surface epithelium was markedly decreased. In contrast to the wild type mice, which were born with their eyelids closed, the c-JunΔOSE/ΔOSE mice were born with the eye-open at birth (EOB) phenotype due to failure of embryonic eyelid closure. Both c-JunΔOSE/ΔOSE and Map3k1ΔKD/ΔKD mice displayed the EOB phenotype; however, the Map3k1+/ΔKDc-Jun+/ΔOSE double hemizygous mice were born with closed eyes.
Our results suggest that c-Jun expression in the ocular surface epithelium is essential for embryonic eyelid closure. Lacking genetic complementation between MAP3K1 and c-Jun suggests that these factors may control embryonic eyelid closure through independent mechanisms.
This PDF is available to Subscribers Only