Maternally and zygotically provided Cdx2 have novel and critical roles for early development of the mouse embryo.
Maternally and zygotically provided Cdx2 have novel and critical roles for early development of the mouse embryo.
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DOI：
10.1016/j.ydbio.2010.04.017
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发表时间：
2010-08-01
影响因子：
2.7
通讯作者：
Zernicka-Goetz M
中科院分区：
文献类型：
--
作者：
Jedrusik A;Bruce AW;Tan MH;Leong DE;Skamagki M;Yao M;Zernicka-Goetz M
在小鼠胚胎中，极化的卵裂球的分裂将极细胞分配给外部，将无泡细胞分配给内部位置，从而启动了第一个细胞命运的决定。随后，外层细胞分化为滋养外胚层，而内层细胞保持多能性，成为胚泡的内细胞团(ICM)。排除滋养外胚层特异性转录因子CDX2的合子表达会导致胚泡腔的维持出现缺陷，这表明它只参与滋养外胚层形成的晚期。然而，我们现在发现，小鼠胚胎也有母体提供的CDX2信使核糖核酸。此外，三种独立的方法dsRNAi、siRNAi和吗啉寡核苷酸在受精后立即耗尽母体和受精卵的CDx2，导致发育停滞的时间比预期的要早得多，因为只消除受精卵的CDx2。这种发育停滞与细胞极化缺陷有关，反映在细胞极性分子的表达和定位上，如Par3和aPKC，以及8-和16-细胞阶段的细胞紧凑。缺乏CDX2的细胞发育迟缓，细胞周期长度增加，细胞分裂不规则，细胞凋亡率增加。虽然一些耗尽镉的胚胎会引发空化，但空化不能维持。此外，滋养外胚层特异性基因GATA3和eome以及Troma1识别的滋养外胚层特异性细胞角蛋白中间丝的表达大大减少或检测不到。综上所述，我们的结果表明，CDX2参与了导致滋养外胚层特化的两个步骤：8-细胞期和16-细胞期卵裂球的适当极化，然后维持滋养外胚层特定谱系的分化。
Divisions of polarised blastomeres that allocate polar cells to outer and apolar cells to inner positions initiate the first cell fate decision in the mouse embryo. Subsequently, outer cells differentiate into trophectoderm while inner cells retain pluripotency to become inner cell mass (ICM) of the blastocyst. Elimination of zygotic expression of trophectoderm-specific transcription factor Cdx2 leads to defects in the maintenance of the blastocyst cavity, suggesting that it participates only in the late stage of trophectoderm formation. However, we now find that mouse embryos also have a maternally provided pool of Cdx2 mRNA. Moreover, depletion of both maternal and zygotic Cdx2 from immediately after fertilization by three independent approaches, dsRNAi, siRNAi and morpholino oligonucleotides, leads to developmental arrest at much earlier stages than expected from elimination of only zygotic Cdx2. This developmental arrest is associated with defects in cell polarisation, reflected by expression and localisation of cell polarity molecules such as Par3 and aPKC and cell compaction at the 8- and 16-cell stages. Cells deprived of Cdx2 show delayed development with increased cell cycle length, irregular cell division and increased incidence of apoptosis. Although some Cdx2-depleted embryos initiate cavitation, the cavity cannot be maintained. Furthermore, expression of trophectoderm-specific genes, Gata3 and Eomes, and also the trophectoderm-specific cytokeratin intermediate filament, recognised by Troma1, are greatly reduced or undetectable. Taken together, our results indicate that Cdx2 participates in two steps leading to trophectoderm specification: appropriate polarisation of blastomeres at the 8- and 16-cell stage and then the maintenance of trophectoderm lineage-specific differentiation.
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影响因子：
4.6
作者：
Strumpf, D;Mao, CA;Rossant, J
通讯作者：
Rossant, J
组蛋白精氨酸甲基化调节早期小鼠胚胎中的多能性。
影响因子：
64.8
作者：
Torres-Padilla, Maria-Elena;Parfitt, David-Emlyn;Kouzarides, Tony;Zernicka-Goetz, Magdalena
通讯作者：
Zernicka-Goetz, Magdalena
影响因子：
11.8
作者：
Chazaud, Claire;Yamanaka, Yojiro;Rossant, Janet
通讯作者：
Rossant, Janet
影响因子：
10.5
作者：
Jedrusik, Agnieszka;Parfitt, David-Emlyn;Zernicka-Goetz, Magdalena
通讯作者：
Zernicka-Goetz, Magdalena
影响因子：
64.5
作者：
Niwa, H;Toyooka, T;Rossant, J
通讯作者：
Rossant, J