Initiation of Hippo signaling is linked to polarity rather than to cell position in the pre-implantation mouse embryo
Initiation of Hippo signaling is linked to polarity rather than to cell position in the pre-implantation mouse embryo
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DOI：
10.1242/dev.107276
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发表时间：
2014-07-01
期刊：
影响因子：
4.6
通讯作者：
Yamanaka, Yojiro
中科院分区：
文献类型：
--
作者：
Anani, Shihadeh;Bhat, Shivani;Yamanaka, Yojiro
在小鼠胚胎中，在8-16细胞分裂期间的不对称分裂产生两种细胞类型，极性和非极性细胞，它们分别被分配到外部和内部位置。这种外/内构型是前两种细胞谱系形成的第一个迹象：滋养外胚层（TE）和内细胞团（ICM）。外极细胞变成TE，产生胎盘，而内非极细胞变成ICM，产生胚胎和卵黄囊。在这里，我们分析了8-16细胞分裂期间不对称分裂的频率，并评估了细胞极性、细胞和核位置与Hippo信号激活（在16细胞胚胎中启动谱系特异性基因表达的途径）之间的关系。虽然每个胚胎不对称分裂的频率不同，但我们发现在大多数胚胎中超过六个卵裂球不对称分裂。有趣的是，在16细胞胚胎中，许多非极性细胞位于外部位置，而只有一个或两个非极性细胞位于内部位置。活体成像分析表明，外部非极细胞最终被周围的极细胞内化。使用分离的8-细胞卵裂球，我们仔细分析了非极性细胞的内化过程，发现非极性细胞皮质张力高于极性细胞的迹象。最后，我们发现非极性细胞在采取内部位置之前激活Hippo信号。我们的研究结果表明，极性和非极性细胞有内在的差异，建立外/内配置和差异调节海马信号激活谱系特异性基因表达程序。
In the mouse embryo, asymmetric divisions during the 8-16 cell division generate two cell types, polar and apolar cells, that are allocated to outer and inner positions, respectively. This outer/inner configuration is the first sign of the formation of the first two cell lineages: trophectoderm (TE) and inner cell mass (ICM). Outer polar cells become TE and give rise to the placenta, whereas inner apolar cells become ICM and give rise to the embryo proper and yolk sac. Here, we analyze the frequency of asymmetric divisions during the 8-16 cell division and assess the relationships between cell polarity, cell and nuclear position, and Hippo signaling activation, the pathway that initiates lineage-specific gene expression in 16-cell embryos. Although the frequency of asymmetric divisions varied in each embryo, we found that more than six blastomeres divided asymmetrically in most embryos. Interestingly, many apolar cells in 16-cell embryos were located at outer positions, whereas only one or two apolar cells were located at inner positions. Live imaging analysis showed that outer apolar cells were eventually internalized by surrounding polar cells. Using isolated 8-cell blastomeres, we carefully analyzed the internalization process of apolar cells and found indications of higher cortical tension in apolar cells than in polar cells. Last, we found that apolar cells activate Hippo signaling prior to taking inner positions. Our results suggest that polar and apolar cells have intrinsic differences that establish outer/inner configuration and differentially regulate Hippo signaling to activate lineage-specific gene expression programs.