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首页> 外文期刊>Development >Gene replacement reveals a specific role for E-cadherin in the formation of a functional trophectoderm.
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Gene replacement reveals a specific role for E-cadherin in the formation of a functional trophectoderm.

机译：基因替换揭示了E-钙粘蛋白在功能性滋养外胚层形成中的特定作用。

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During mammalian embryogenesis the trophectoderm represents the first epithelial structure formed. The cell adhesion molecule E-cadherin is ultimately necessary for the transition from compacted morula to the formation of the blastocyst to ensure correct establishment of adhesion junctions in the trophectoderm. Here, we analyzed to what extent E-cadherin confers unique adhesion and signaling properties in trophectoderm formation in vivo. Using a gene replacement approach, we introduced N-cadherin cDNA into the E-cadherin genomic locus. We show that the expression of N-cadherin driven from the E-cadherin locus reflects the expression pattern of endogenous E-cadherin. Heterozygous mice co-expressing E- and N-cadherin are vital and show normal embryonic development. Interestingly, N-cadherin homozygous mutant embryos phenocopy E-cadherin-null mutant embryos. Upon removal of the maternal E-cadherin, we demonstrate that N-cadherin is able to provide sufficient cellular adhesion to mediate morula compaction,but is insufficient for the subsequent formation of a fully polarized functional trophectoderm. When ES cells were isolated from N-cadherin homozygous mutant embryos and teratomas were produced, these ES cells differentiated into a large variety of tissue-like structures. Importantly, different epithelial-like structures expressing N-cadherin were formed, including respiratory epithelia, squamous epithelia with signs of keratinization and secretory epithelia with goblet cells. Thus, N-cadherin can maintain epithelia in differentiating ES cells, but not during the formation of the trophectoderm. Our results point to a specific and unique function for E-cadherin during mouse preimplantation development.
机译：在哺乳动物胚胎发生期间，滋养外胚层代表形成的第一个上皮结构。细胞粘附分子E-钙粘着蛋白对于从紧实的桑ula骨向胚泡的形成过渡是最终必需的，以确保在滋养外胚层中正确建立粘附连接。在这里，我们分析了E-钙粘着蛋白在体内在滋养外胚层形成中赋予独特的粘附和信号传导特性的程度。使用基因替代方法，我们将N-钙粘蛋白cDNA引入E-钙粘蛋白基因组位点。我们表明，从E-钙粘蛋白基因座驱动的N-钙粘蛋白的表达反映了内源性E-钙粘蛋白的表达模式。共表达E-和N-钙粘着蛋白的杂合子小鼠至关重要，并显示出正常的胚胎发育。有趣的是，N-钙粘蛋白纯合突变体胚胎表型为E-钙粘蛋白-无效突变体胚胎。去除母体E-钙粘着蛋白后，我们证明N-钙粘着蛋白能够提供足够的细胞粘附来介导桑ula的紧实，但不足以用于随后形成完全极化的功能性滋养外胚层。当从N-钙粘着蛋白纯合突变体胚胎中分离ES细胞并产生畸胎瘤时，这些ES细胞分化为各种各样的组织样结构。重要的是，形成了表达N-钙粘着蛋白的不同上皮样结构，包括呼吸上皮，具有角质化迹象的鳞状上皮和具有杯状细胞的分泌上皮。因此，N-钙粘着蛋白可以在分化的ES细胞中维持上皮，但在滋养外胚层形成过程中则不能。我们的结果表明，在小鼠植入前发育过程中，E-钙黏着蛋白具有特定而独特的功能。

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