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植入前发育中的细胞间通讯:缝隙连接的作用。

Intercellular communication in preimplantation development: the role of gap junctions.

作者信息

Kidder G M, Winterhager E

机构信息

Departments of Physiology, Obstetrics and Gynaecology, and Paediatrics, The University of Western Ontario, London, Ontario N6A 5C1, Canada.

出版信息

Front Biosci. 2001 May 1;6:D731-6. doi: 10.2741/kidder.

Abstract

Gap junctions are sites where intercellular membrane channels are clustered that allow neighboring cells to pass small molecules directly between them. Gap junctional intercellular communication has been implicated in a variety of human diseases. Gap junction channels are assembled from a large family of proteins called connexins with each type of channel having some unique properties. Preimplantation mouse and rat embryos express multiple connexins and thus potentially contain many types of gap junction channels. Based on experiments focussing on connexin43, gap junction assembly in the mouse begins during compaction in the 8-cell stage and is post-translationally regulated. Gene targeting has been used to create mice lacking individual connexins that are expressed in preimplantation embryos, but none of these experiments has yet revealed a necessary role for any single connexin before implantation. Experiments with anti-connexin antibodies and pharmacological blockers of gap junctional coupling have provided conflicting evidence as to the importance of gap junctions for preimplantation development. However, connexin knockouts have revealed important roles for gap junctional coupling in early postimplantation development. It is proposed that expression of multiple connexins in the blastocyst could prepare the implanting conceptus for rapid diversification of cell types during gastrulation and development of the placenta.

摘要

间隙连接是细胞间膜通道聚集的位点,它允许相邻细胞之间直接传递小分子。间隙连接介导的细胞间通讯与多种人类疾病有关。间隙连接通道由一大类称为连接蛋白的蛋白质组装而成,每种类型的通道都具有一些独特的特性。植入前的小鼠和大鼠胚胎表达多种连接蛋白,因此可能含有多种类型的间隙连接通道。基于针对连接蛋白43的实验,小鼠中的间隙连接组装在8细胞期的致密化过程中开始,并受到翻译后调控。基因打靶已被用于创建缺乏在植入前胚胎中表达的单个连接蛋白的小鼠,但这些实验均未揭示任何单个连接蛋白在植入前的必要作用。使用抗连接蛋白抗体和间隙连接偶联的药理学阻滞剂进行的实验,就间隙连接对植入前发育的重要性提供了相互矛盾的证据。然而,连接蛋白基因敲除已揭示间隙连接偶联在植入后早期发育中的重要作用。有人提出,囊胚中多种连接蛋白的表达可以使着床的孕体为原肠胚形成和胎盘发育过程中细胞类型的快速多样化做好准备。

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