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Jin Woo Kim, Kyeong Hwan Moon; Growth coordination of mouse eye compartments by NF2-Hippo-Yap/Taz signaling cascade. Invest. Ophthalmol. Vis. Sci. 2018;59(9):596.
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Optic tissues drived from the optic neuroepithelium exhibit different physiological properties during development. The cell population in the retina has a higher proliferative potential than cells in the other two adjacent compartments, the ciliary margin (CM) and retinal pigment epithelium (RPE). It suggests the presence of regulators that are differentially expressed or activated in each optic neuroepithelial compartment. We investigated the roles of neurofibromin 2 (Nf2), which is enriched in the CM and RPE but not in the retina, in establishing differential growth of the optic neuroepithelial compartments.
To investigate region-specific functions of Nf2 in mouse optic neuroepithelial compartments, Nf2-flox mice were bred with various mice expressing Cre recombinases in specific optic compartments. The identity of Nf2-deficient cells as well as the morphology and anatomical features of the mouse eyes were examined. Especially, proliferation of cells in each compartment was determined by BrdU-labeling.
The loss of mouse Nf2 in mouse optic neuroepithelial compartments causes autonomous hyperplasia in each compartment. The hyperplastic ocular phenotypes were largely suppressed by heterozygous deletion of Yap and Taz, key targets of the Nf2-Hippo signaling pathway. We found that, in addition to feedback transcriptional regulation of Nf2 by Yap/Taz in the CM, activation of Nf2 expression by Mitf in the RPE and suppression by Sox2 in retinal progenitor cells are necessary for the differential growth of the corresponding cell populations.
Our study reveals that Nf2 is a key player that orchestrates the differential growth of optic neuroepithelial compartments during vertebrate eye development.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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