Fig. 2: TRULI mediates activation of Yap and proliferation of supporting cells.
a A timeline depicts the pattern of the experiments shown in the indicated subsequent panels. Treatment of murine utricles with TRULI is initiated at the outset. b TRULI exposure drives Yap into the nuclei of utricular supporting cells. c In vitro exposure to TRULI for 5 days elicits proliferation of supporting cells, as measured by the incorporation of EdU. Verteporfin, an inhibitor of the Yap–Tead interaction, drastically reduces this effect. d In a whisker box plot, the nuclear localization of Yap is quantified as a ratio to the constitutively expressed protein Sall2 (p = 2.683 × 10−170, by an unpaired, two-tailed t-test, n = 570 control nuclei and 680 treated nuclei). e The number of EdU-positive cells per utricle increases with TRULI (p = 0.0309 by one-way ANOVA, control n = 2, TRULI n = 3, verteporfin plus TRULI n = 2, mean ± SEM). f Conditional deletion of Yap by tamoxifen administration to SOX2-CreER Yapfl/fl (Yap CKO) animals at P1, 7 or 14 days prior to explanation, decreases the number of Sox2 (red) and EdU (white) doubly positive supporting cells compared to Cre-negative Yapfl/fl (WT) littermates. g Quantification of the number of EdU-positive cells in panel f demonstrates that decrease in supporting-cell proliferation is statistically significant (p = 1.2798 × 10−7 by one-way ANOVA; n = 3 for wild-type control and Yap CKO at 7 days; n = 4 for TRULI treatment; n = 6 for Yap CKO at 10 days and TRULI, mean ± SEM). See also Supplementary Fig. 2.
