Allocation of inner cells to epiblast vs primitive endoderm in the mouse embryo is biased but not determined by the round of asymmetric divisions (8 → 16-and 16 → 32-cells)
Allocation of inner cells to epiblast vs primitive endoderm in the mouse embryo is biased but not determined by the round of asymmetric divisions (8 → 16-and 16 → 32-cells)
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DOI：
10.1016/j.ydbio.2013.09.008
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发表时间：
2014-01-01
影响因子：
2.7
通讯作者：
Suwinska, Aneta
中科院分区：
文献类型：
--
作者：
Krupa, Magdalena;Mazur, Ewa;Suwinska, Aneta
外胚层（EPI）和原始内胚层（PE）分别构成胚泡内细胞团（ICM）的深层和表层，它们构成未来胚胎体和卵黄囊的基础。在到达ICM内的目标定位之前，显示不同谱系特异性标记的PE和EPI前体细胞随机混合。由于ICM细胞在8 -> 16（初级内细胞）和16 -> 32细胞阶段（次级内细胞）的两轮连续不对称分裂中产生，因此已经表明内细胞的命运（决定成为EPI或PE）可能取决于它们起源的时间。我们的方法的双重标记的胚胎，使我们能够区分初级和次级内细胞最终有助于ICM。我们的研究结果表明，在32细胞期胚胎中存在两代内细胞是ICM内异质性的来源。我们发现了一些偏见有关的FGF 4和FGFR 2表达水平之间的初级和次级内细胞，导致不同数量的细胞表达这些基因。对使用不同比例的内部细胞被外部细胞包围而构建的实验聚集体的分析表明，细胞的命运并不仅仅取决于它们产生的时间，而且还取决于每一波不对称分裂中产生的细胞数量。总之，所观察到的调节胚胎内外细胞与内细胞比例的调节机制可能由FGF信号传导介导。(C)2013 Elsevier Inc. All rights reserved.
The epiblast (EPI) and the primitive endoderm (PE), which constitute foundations for the future embryo body and yolk sac, build respectively deep and surface layers of the inner cell mass (ICM) of the blastocyst. Before reaching their target localization within the ICM, the PE and EPI precursor cells, which display distinct lineage-specific markers, are intermingled randomly. Since the ICM cells are produced in two successive rounds of asymmetric divisions at the 8 -> 16 (primary inner cells) and 16 -> 32 cell stage (secondary inner cells) it has been suggested that the fate of inner cells (decision to become EPI or PE) may depend on the time of their origin. Our method of dual labeling of embryos allowed us to distinguish between primary and secondary inner cells contributing ultimately to ICM. Our results show that the presence of two generations of inner cells in the 32-cell stage embryo is the source of heterogeneity within the ICM. We found some bias concerning the level of Fgf4 and Fgfr2 expression between primary and secondary inner cells, resulting from the distinct number of cells expressing these genes. Analysis of experimental aggregates constructed using different ratios of inner cells surrounded by outer cells revealed that the fate of cells does not depend exclusively on the timing of their generation, but also on the number of cells generated in each wave of asymmetric division. Taking together, the observed regulatory mechanism adjusting the proportion of outer to inner cells within the embryo may be mediated by FGF signaling. (C) 2013 Elsevier Inc. All rights reserved.