Role of Cdx2 and cell polarity in cell allocation and specification of trophectoderm and inner cell mass in the mouse embryo
Role of Cdx2 and cell polarity in cell allocation and specification of trophectoderm and inner cell mass in the mouse embryo
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DOI：
10.1101/gad.486108
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发表时间：
2008-10-01
影响因子：
10.5
通讯作者：
Zernicka-Goetz, Magdalena
中科院分区：
文献类型：
--
作者：
Jedrusik, Agnieszka;Parfitt, David-Emlyn;Zernicka-Goetz, Magdalena
滋养外胚层和内细胞团（ICM）谱系的发生分为两个阶段。它是通过8细胞和16细胞卵裂球的不对称分裂启动的，这些分裂将细胞分配到内部和外部位置，每个位置具有不同的发育命运。外部细胞成为致力于滋养外胚层在囊胚阶段通过Cdx2的活动，但在这里，我们表明，Cdx2也可以采取行动，影响细胞分配。增加单个卵裂球中的Cdx2水平促进对称分裂，从而将更多的细胞分配给滋养外胚层，而减少Cdx2促进不对称分裂，从而促进ICM。此外，Cdx2 mRNA和蛋白水平在八细胞期是异质的。这种异质性取决于细胞来源，并具有发育后果。Cdx2表达在具有不受限制的发育潜力的细胞中是最小的，其优先贡献于ICM，并且在具有降低的潜力的细胞中是最大的，其贡献于滋养外胚层。最后，我们描述了细胞极性和Cdx2之间的相互促进的关系：Cdx2通过上调aPKC影响细胞极性，但细胞极性也通过极化卵裂球中Cdx2 mRNA的不对称分布影响Cdx2。因此，细胞内外产生的分裂在细胞命运指令方面是真正不对称的。这两种相互作用的作用确保了胚泡阶段稳定的外上皮的产生。
Genesis of the trophectoderm and inner cell mass (ICM) lineages occurs in two stages. It is initiated via asymmetric divisions of eight- and 16-cell blastomeres that allocate cells to inner and outer positions, each with different developmental fates. Outside cells become committed to the trophectoderm at the blastocyst stage through Cdx2 activity, but here we show that Cdx2 can also act earlier to influence cell allocation. Increasing Cdx2 levels in individual blastomeres promotes symmetric divisions, thereby allocating more cells to the trophectoderm, whereas reducing Cdx2 promotes asymmetric divisions and consequently contribution to the ICM. Furthermore, both Cdx2 mRNA and protein levels are heterogeneous at the eight- cell stage. This heterogeneity depends on cell origin and has developmental consequences. Cdx2 expression is minimal in cells with unrestricted developmental potential that contribute preferentially to the ICM and is maximal in cells with reduced potential that contribute more to the trophectoderm. Finally, we describe a mutually reinforcing relationship between cellular polarity and Cdx2: Cdx2 influences cell polarity by up-regulating aPKC, but cell polarity also influences Cdx2 through asymmetric distribution of Cdx2 mRNA in polarized blastomeres. Thus, divisions generating inside and outside cells are truly asymmetric with respect to cell fate instructions. These two interacting effects ensure the generation of a stable outer epithelium by the blastocyst stage.