The Apical Domain Is Required and Sufficient for the First Lineage Segregation in the Mouse Embryo.
The Apical Domain Is Required and Sufficient for the First Lineage Segregation in the Mouse Embryo.
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DOI：
10.1016/j.devcel.2017.01.006
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发表时间：
2017-02-06
影响因子：
11.8
通讯作者：
Hiiragi T
中科院分区：
文献类型：
--
作者：
Korotkevich E;Niwayama R;Courtois A;Friese S;Berger N;Buchholz F;Hiiragi T
哺乳动物的发育始于胚外滋养外胚层与胚泡中胚胎谱系的分离。虽然细胞极性和粘附起着关键作用，但驱动这种谱系分离的决定性线索仍然难以捉摸。在这里，为了研究对称性破缺，我们使用了一个简化的系统，其中孤立的卵裂球重演了第一谱系分离。我们发现，在8-细胞期胚胎，顶端域招聘纺锤极，以确保其分化后的分布。继承顶端结构域的子细胞采用滋养外胚层的命运。然而，非极性子细胞的命运取决于它们在胚胎中的位置是否有利于Cdh 1-独立的细胞接触形成顶端结构域。最后，我们开发的方法移植顶端域，并表明，该域的收购不仅是必需的，但也足够的第一谱系隔离。因此，我们提供了机制的理解，调和以前的模型对称性破缺小鼠的发展。建立了一个简化系统来研究小鼠发育过程中的对称性破缺8细胞期卵裂球获得自组织顶端结构域的能力顶端结构域是第一谱系分离所必需的，并且对于第一谱系分离是足够的接触不对称性指定细胞命运，导致自组织胚胎图案化Korotkevich et al.使用简化的系统来研究小鼠早期发育中的对称性破坏，并表明Cdh 1独立的接触不对称性指导了时间控制的顶端结构域的形成，这对于分离第一细胞谱系是必要的和足够的。
Mammalian development begins with segregation of the extra-embryonic trophectoderm from the embryonic lineage in the blastocyst. While cell polarity and adhesion play key roles, the decisive cue driving this lineage segregation remains elusive. Here, to study symmetry breaking, we use a reduced system in which isolated blastomeres recapitulate the first lineage segregation. We find that in the 8-cell stage embryo, the apical domain recruits a spindle pole to ensure its differential distribution upon division. Daughter cells that inherit the apical domain adopt trophectoderm fate. However, the fate of apolar daughter cells depends on whether their position within the embryo facilitates apical domain formation by Cdh1-independent cell contact. Finally, we develop methods for transplanting apical domains and show that acquisition of this domain is not only required but also sufficient for the first lineage segregation. Thus, we provide mechanistic understanding that reconciles previous models for symmetry breaking in mouse development. A reduced system was established to study symmetry breaking in mouse development 8-cell stage blastomeres acquire the capacity to self-organize the apical domain The apical domain is required and sufficient for the first lineage segregation Contact asymmetry specifies cell fate, leading to self-organized embryo patterning Korotkevich et al. use a reduced system to study symmetry breaking in early mouse development and show that Cdh1-independent contact asymmetry directs temporally controlled apical domain formation, which is necessary and sufficient for segregating the first cell lineages.