Active cell movements coupled to positional induction are involved in lineage segregation in the mouse blastocyst.

Active cell movements coupled to positional induction are involved in lineage segregation in the mouse blastocyst.
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DOI:
10.1016/j.ydbio.2009.04.036
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发表时间:
2009-07-15
影响因子:
2.7
通讯作者:
Zernicka-Goetz, Magdalena
Zernicka-Goetz, Magdalena
中科院分区:
生物学3区
文献类型:
--
作者:
Meilhac, Sigolene M.;Adams, Richard J.;Morris, Samantha A.;Danckaert, Anne;Le Garrec, Jean-Francois;Zernicka-Goetz, Magdalena

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在小鼠胚泡中,内细胞团(ICM)的一些细胞在表面发育成原始内胚层(PE),而更深的细胞形成上胚层。目前尚不清楚细胞的位置是否决定了它们的命运,例如基因表达是否根据细胞位置进行调整,或者细胞是否预先指定在随机位置,然后进行排序。我们已经跟踪并表征了从早期到晚期囊胚阶段的所有ICM细胞的动态。在H2 B-EGFP胚胎中的延时显微镜显示,大部分ICM细胞在表面和更深的隔室之间改变位置。这种细胞运动的大部分依赖于肌动蛋白,并与细胞突起有关。我们还发现,虽然大多数细胞的前体只有一个谱系,一些引起的两个,表明谱系分离是不完整的早期ICM。最后,改变PE标志物Gata 6的表达水平揭示了它在表面细胞中是必需的,但不足以重新定位更深的细胞。我们提供的证据表明,已知在表面ICM中表达的Wnt 9A有助于Gata 6表达细胞的重新定位。将这些实验结果与计算机建模相结合表明,PE的形成涉及细胞分选运动和位置依赖性诱导。
In the mouse blastocyst, some cells of the inner cell mass (ICM) develop into primitive endoderm (PE) at the surface, while deeper cells form the epiblast. It remained unclear whether the position of cells determines their fate, such that gene expression is adjusted to cell position, or if cells are pre-specified at random positions and then sort. We have tracked and characterised dynamics of all ICM cells from the early to late blastocyst stage. Time-lapse microscopy in H2B-EGFP embryos shows that a large proportion of ICM cells change position between the surface and deeper compartments. Most of this cell movement depends on actin and is associated with cell protrusions. We also find that while most cells are precursors for only one lineage, some give rise to both, indicating that lineage segregation is not complete in the early ICM. Finally, changing the expression levels of the PE marker Gata6 reveals that it is required in surface cells but not sufficient for the re-positioning of deeper cells. We provide evidence that Wnt9A, known to be expressed in the surface ICM, facilitates re-positioning of Gata6-expressing cells. Combining these experimental results with computer modelling suggests that PE formation involves both cell sorting movements and position-dependent induction.
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