Position- and polarity-dependent Hippo signaling regulates cell fates in preimplantation mouse embryos.
Position- and polarity-dependent Hippo signaling regulates cell fates in preimplantation mouse embryos.
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DOI：
10.1016/j.semcdb.2015.05.003
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发表时间：
2015-12
影响因子：
7.3
通讯作者：
H. Sasaki
中科院分区：
文献类型：
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作者：
H. Sasaki
在植入前阶段，小鼠胚胎在早期囊胚形成时建立了两种细胞谱系：滋养外胚层(TE)和内细胞团(ICM)。历史模型提出，这两个谱系的建立取决于细胞在胚胎中的位置(例如，位置模型)或沿顶基轴线的细胞极化(例如，极性模型)。最近的发现表明，河马信号通路在细胞命运指定过程中起着核心作用：内、外细胞中活跃和非活跃的河马信号分别促进ICM和TE命运。细胞间黏附被激活，而基底部极化抑制河马信号，这些过程的结合决定了32细胞期胚胎中河马信号通路的空间调控激活。因此，有实验证据支持位置模型和极性模型。在分子水平上，内(脱泡)细胞中Hippo途径成分Angiomotin在黏附连接(AJs)处的磷酸化激活了LATS蛋白激酶，并触发了Hippo信号。然而，在外部细胞中，细胞极化隔离了基底外侧AJ，并抑制了河马通路的激活。其他机制，包括细胞不对称分裂和Notch信号，也在胚胎发育的调节中发挥重要作用。在这篇综述中，我讨论了在细胞命运指定过程中，这些机制如何与河马信号通路合作。
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.