Department of Bioengineering, University of Washington, Seattle, Washington, USA.
Dev Dyn. 2013 Sep;242(9):1110-20. doi: 10.1002/dvdy.23991. Epub 2013 Jun 25.
Although successful implantation is required for development in placental mammals, the molecular and morphogenetic events that define peri-implantation remain largely unexplored.
Here we present detailed morphological and immunohistochemical analysis of mouse embryos between embryonic day 3.75 and 5.25 of gestation, during the implantation process in vivo. We examined expression patterns of key transcription factors (Sox2, Oct4, Nanog, Cdx2, Gata6, Sox17, and Yy1) during pre- and postimplantation development. Additionally, we examined morphogenetic changes through analysis of ZO-1, Laminin, and E-Cadherin localization. The results presented reveal novel changes in gene expression and morphogenetic events during peri-implantation in utero. Here we show: (1) molecular and morphological changes in primitive endoderm cells as they transition from a salt and pepper distribution to a sheet covering the inner cell mass; (2) tissue-specific GATA6 levels; and (3) a striking pattern of SOX17 that is suggestive of a functional role either directing or permitting implantation at specific sites in the uterine epithelium.
A growing number of knockout mice display peri-implantation lethality, and the data presented herein identify key morphogenetic landmarks that can be used to characterize mutant phenotypes, as well as further our basic understanding of peri-implantation development.
尽管胎盘哺乳动物的发育需要成功的着床,但定义着床前后的分子和形态发生事件在很大程度上仍未得到探索。
在这里,我们呈现了在体内着床过程中,胚胎第 3.75 天至第 5.25 天之间的小鼠胚胎的详细形态学和免疫组织化学分析。我们检查了关键转录因子(Sox2、Oct4、Nanog、Cdx2、Gata6、Sox17 和 Yy1)在着床前和着床后发育过程中的表达模式。此外,我们通过分析 ZO-1、层粘连蛋白和 E-钙黏蛋白的定位来检查形态发生变化。所呈现的结果揭示了在子宫内着床前后发育过程中基因表达和形态发生的新变化。在这里,我们展示了:(1)原始内胚层细胞从盐和胡椒分布过渡到覆盖内细胞团的薄片时的分子和形态变化;(2)组织特异性的 GATA6 水平;(3)SOX17 的惊人模式,提示其在子宫上皮的特定部位指导或允许着床具有功能作用。
越来越多的基因敲除小鼠表现出着床前后的致死性,本文所呈现的数据确定了关键的形态发生标志,可以用于描述突变表型,并进一步加深我们对着床前后发育的基本理解。