Position-Dependent Hippo Signaling Controls Cell Fates in Preimplantation Mouse Embryos

Abstract

During preimplantation mouse development, embryos establish two distinct cell lineages by the time of early blastocyst formation: the trophectoderm (TE) and the inner cell mass (ICM). Historically, the importance of cell position within the embryo (inside–outside model) and apico-basal difference, known as cell polarity (polarity model), were suggested for establishment of the two lineages. In this review, I describe the mechanisms of cell fate specification in preimplantation embryos as an example of cell fate control by position-dependent Hippo signaling. Cell–cell adhesion and cell polarity activate and suppress Hippo signaling, respectively, and their combination establishes position-dependent Hippo signaling. Thus, both inside–outside and polarity models are supported. At the molecular level, phosphorylation of the adherens junctions (AJs)-associated Hippo signal component, angiomotin (Amot), activates Lats protein kinase and triggers Hippo signaling. Although this mechanism operates in the AJs of the apolar inner cells, in the outer cells, cell polarity sequesters Amot from basolateral AJs and inactivates the Hippo pathway. Thus, in preimplantation embryos, the cells utilize positional information for proper cell fate control through Hippo signaling. I also discuss the roles of Hippo signaling in regulation of development.