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Fig. 3. Nf2 expression is differentially regulated in the optic neuroepithelial continuum, which shows regional differentiation of proliferation rates. In the post-mitotic RPE, Mitf induces Nf2 expression by directly binding to upstream sequences of the Nf2 gene, triggering Hippo signaling and thereby excluding Yap/Taz from the nucleus. In proliferating RPCs, Sox2 inhibits the expression of Nf2 and, as a consequence, impedes Hippo signaling activity. In CM progenitors, which have the potential to give rise to RPCs and RPE in addition to developing locally into the CB and iris, Yap/Taz is localized to the nucleus, where it induces the expression of Nf2, thereby establishing the NF2-Hippo-Yap/Taz signaling cascade. This feedback regulatory circuit maintains a level of proliferation in CM cells intermediate between that of the RPE and RPCs.
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