Tight junctions containing claudin 4 and 6 are essential for blastocyst formation in preimplantation mouse embryos
Tight junctions containing claudin 4 and 6 are essential for blastocyst formation in preimplantation mouse embryos
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DOI：
10.1016/j.ydbio.2007.09.049
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发表时间：
2007-12-15
影响因子：
2.7
通讯作者：
Furuse, Mikio
中科院分区：
文献类型：
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作者：
Moriwaki, Kazumasa;Tsukita, Shoichiro;Furuse, Mikio
滋养外胚层（TE）是哺乳动物早期发育过程中产生的第一个上皮细胞。TE作为屏障将内细胞团与子宫环境隔离，并通过升高的静水压力提供胚泡的膨胀度。在这项研究中，我们调查的作用，紧密连接（TJ）的屏障功能的TE在小鼠囊胚形成。RT-PCR和免疫染色显示，小鼠TE表达至少claudin 4，6，和7中的24个成员的claudin基因家族，编码的结构和功能成分的TJ。当胚胎培养在GST融合的C-末端一半的产气荚膜梭菌肠毒素（GST-C-CPE），多肽具有抑制活性的claudin 4和6的存在下，正常的囊胚形成显着抑制;胚胎没有或未成熟的囊胚腔没有扩张，卵裂球呈圆形。在这些胚胎中，紧密连接蛋白4和6蛋白不存在于TJ中，TE的屏障功能被破坏;然而，被认为参与胚泡形成的Na+/K+-ATP酶α 1亚基和水通道蛋白3的基底外侧定位似乎正常。这些结果清楚地表明，TE中TJ的屏障功能是正常胚泡形成所必需的。(c)2007年爱思唯尔公司All rights reserved.
The trophectoderm (TE) is the first epithelium to be generated during mammalian early development. The TE works as a barrier that isolates the inner cell mass from the uterine environment and provides the turgidity of the blastocyst through elevated hydrostatic pressure. In this study, we investigated the role of tight junctions (TJs) in the barrier function of the TE during mouse blastocyst formation. RT-PCR and immunostaining revealed that the mouse TE expressed at least claudin 4, 6, and 7 among the 24 members of the claudin gene family, which encode structural and functional constituents of TJs. When embryos were cultured in the presence of a GST-fused C-terminal half of Clostridium perfringens enterotoxin (GST-C-CPE), a polypeptide with inhibitory activity to claudin 4 and 6, normal blastocyst formation was remarkably inhibited; the embryos had no or an immature blastocoel cavity without expansion, and blastomeres showed a rounded shape. In these embryos, claudin 4 and 6 proteins were absent from TJs and the barrier function of the TE was disrupted; however the basolateral localization of the Na+/K+-ATPase alpha 1 subunit and aquaporin 3, which are thought to be involved in blastocyst formation, appeared normal. These results clearly demonstrate that the barrier function of TJs in the TE is required for normal blastocyst formation. (c) 2007 Elsevier Inc. All rights reserved.