title: Position- and polarity-dependent Hippo signaling regulates cell fates in preimplantation mouse embryos.
abstract: During the preimplantation stage, mouse embryos establish two cell lineages by the time of early blastocyst formation: the trophectoderm (TE) and the inner cell mass (ICM). Historical models have proposed that the establishment of these two lineages depends on the cell position within the embryo (e.g., the positional model) or cell polarization along the apicobasal axis (e.g., the polarity model). Recent findings have revealed that the Hippo signaling pathway plays a central role in the cell fate-specification process: active and inactive Hippo signaling in the inner and outer cells promote ICM and TE fates, respectively. Intercellular adhesion activates, while apicobasal polarization suppresses Hippo signaling, and a combination of these processes determines the spatially regulated activation of the Hippo pathway in 32-cell-stage embryos. Therefore, there is experimental evidence in favor of both positional and polarity models. At the molecular level, phosphorylation of the Hippo-pathway component angiomotin at adherens junctions (AJs) in the inner (apolar) cells activates the Lats protein kinase and triggers Hippo signaling. In the outer cells, however, cell polarization sequesters Amot from basolateral AJs and suppresses activation of the Hippo pathway. Other mechanisms, including asymmetric cell division and Notch signaling, also play important roles in the regulation of embryonic development. In this review, I discuss how these mechanisms cooperate with the Hippo signaling pathway during cell fate-specification processes.
authors.affiliation: Laboratory for Embryogenesis, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: sasaki@fbs.osaka-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D000090683:Hippo Signaling Pathway; D051379:Mice; D008954:Models, Biological; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000090742:Serine-Threonine Kinase 3; D015398:Signal Transduction / Q000502:physiology*; D000099317:Hippo Kinases
chemical_list: D017346:Protein Serine-Threonine Kinases; D000090742:Serine-Threonine Kinase 3; C490660:Stk4 protein, mouse; D000099317:Hippo Kinases; C490818:Stk3 protein, mouse
keywords: Cell fate specification; Hippo signaling pathway; Preimplantation mouse embryo; Trophectoderm