アクティブボード・２０１３年１２月
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研究発表を行った学会；
・第４６回日本発生生物学会年会
　２０１３年　５月２８日〜３１日（松江）
タイトル；Cell polarity suppresses Hippo signaling through the regulation of Angiomotin distribution in preimplantation mouse embryos.
発表者；平手　良和　氏
　　　（熊本大学　発生医学研究所　分化制御分野）
Abstract；
In preimplantation mouse embryos, cell fate determination is dependent on cell position, of which underlying mechanisms have long been a matter of debate. We previously revealed that the cell fate is regulated by the strength of Hippo signaling. Strong signaling of the inner cells leads to the inner cell mass, whereas weak signaling of the outer cells leads to the trophectoderm. Here, we show that cell polarity of the outer cells suppressed Hippo signaling through the regulation of a scaffolding protein Angiomotin (Amot) subcellular localization. In the inner cells, which were apolar and have strong Hippo signaling, Amot was localized to the adherens junctions in the inner cells, where Amot interacted with E-cadherin. Amot also interacted with Lats2, a core kinase of the Hippo pathway. Therefore, it was likely that cell-cell contact information was transferred from E-cadherin to Amot and then it activated the Hippo pathway via interaction with Lats2. In contrast, in the outer cells, cell polarity restricted the distribution of Amot to the apical membrane and tight junctions, resulting in sequestration of Amot from the adherens junctions. Thus, Hippo signaling was almost missing in the outer cells. Domain analysis revealed that both coiled-coil domain and N-terminal region were critical for interaction with E-cadherin and for Hippo-pathway activation. The proposed mechanisms convert positional information into differential Hippo signaling and establish distinct cell fates.