Figure 3. The molecular basis of differential Hippo signaling in preimplantation embryos. (A) Amot KO enhances Hippo signaling in the outer cells as shown by an increased level of phosphorylated Yap (p-Yap). The inner cells are encircled by dashed lines in the left panels. The graph shows the mean level of p-Yap in the outer cells of wildtype (wt) (n = 4) and Amot KO (n = 5) embryos. Error bars show the standard error of the mean. These data suggest that Hippo signaling is inhibited at the apical membrane. (B) A model of Hippo pathway regulation in preimplantation embryos. In the inner cells, phosphorylated Amot makes an active complex with Merlin–Lats at the AJs, activating Hippo signaling. In the outer cells, (1) cell polarity factors sequester Amot from the basolateral AJs, thereby attenuating E-cadherin-mediated Hippo signaling. (2) Nonphosphorylated apical Amot makes an inactive complex with Merlin–Lats, which binds cortical F-actin, suppressing Lats activity.