Developmental regulation of integrin expression at the time of implantation in the mouse embryo.
Developmental regulation of integrin expression at the time of implantation in the mouse embryo.
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发表时间：
1993-12
期刊：
影响因子：
4.6
通讯作者：
A. Sutherland;P. Calarco;C. Damsky
中科院分区：
文献类型：
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作者：
A. Sutherland;P. Calarco;C. Damsky
小鼠胚泡的滋养外胚层层在胚泡晚期分化形成侵入性滋养层，其介导胚胎植入子宫壁。滋养层细胞已经发展出侵袭特异性细胞行为的第一个迹象出现在胚胎从透明质膜孵化后约10 - 15小时，此时静止的、非粘附的滋养外胚层细胞启动侵袭活性并变得粘附于细胞外基质。我们先前的发现是滋养层在细胞外基质包被的基质上的生长涉及粘附受体的整联蛋白家族（Sutherland，A. E、Calarco，P. G. Damsky，C. H、1988，J.Cell Biol.106，1331 - 1348）表明，在植入时滋养层粘附和迁移行为的开始可能是由于整联蛋白受体的表达或分布的变化。因此，我们研究了mRNA和蛋白质表达的个别整合素亚基在植入前和围植入期的发展（E0-E7.5）。整合素的基本库，包括纤维连接蛋白（α 5 β 1），层粘连蛋白（α 6B β 1）和玻连蛋白（α v β 3）的受体，在此期间连续表达，而其他五个整合素亚基的表达发育调节。其中三种（α 2，α 6A和α 7）的mRNA首先在晚期囊胚中检测到，与内胚层分化和附着能力的发育一致。另一种（α 1）的mRNA直到滋养层生长开始后才被检测到，这表明其表达可能是通过与基质接触诱导的。在E7.5，三个时间调节的整合素（α 1，apha 6A，α 7），所有这些都可以形成层粘连蛋白的受体，仅在外胎盘锥（分化滋养层）中检测到，因此可能在滋养层粘附和/或分化中发挥特定的作用。由于层粘连蛋白的表达上调蜕膜化子宫间质中响应植入胚胎，我们研究滋养层-层粘连蛋白的相互作用，使用层粘连蛋白片段和整合素抗体，以确定哪些整合素受体参与。滋养层细胞贴附并在层粘连蛋白的E8和P1 '片段上扩散;然而，P1'结合位点在完整的层粘连蛋白中是隐蔽的。与P1 '的相互作用是RGD和α v β 3依赖性的，而在E8上的生长是RGD非依赖性的，并且不被层粘连蛋白受体α 6 β 1的抗体抑制，这表明α 7 β 1是主要的滋养层整联蛋白E8受体。（400字处截断摘要）
The trophectoderm layer of the mouse blastocyst differentiates at the late blastocyst stage to form the invasive trophoblast that mediates implantation of the embryo into the uterine wall. The first sign that trophoblast cells have developed an invasion-specific cell behavior appears about 10-15 hours after the embryo hatches from the zona pellucida, when the quiescent, non-adherent trophectoderm cells initiate protrusive activity and become adhesive to extracellular matrix. Our previous findings that trophoblast outgrowth on extracellular-matrix-coated substrata involves the integrin family of adhesion receptors (Sutherland, A. E., Calarco, P. G. and Damsky, C. H., 1988, J. Cell Biol. 106, 1331-1348), suggested that the onset of trophoblast adhesive and migratory behavior at the time of implantation may be due to changes in expression or distribution of integrin receptors. We have thus examined the mRNA and protein expression of individual integrin subunits during pre- and periimplantation development (E0-E7.5). A basic repertoire of integrins, including receptors for fibronectin (alpha 5 beta 1), laminin (alpha 6B beta 1) and vitronectin (alpha v beta 3), was expressed continuously throughout this period, whereas the expression of five other integrin subunits was developmentally regulated. The mRNA for three of these (alpha 2, alpha 6A and alpha 7) was first detected in the late blastocyst, coincident with endoderm differentiation and development of attachment competence. The mRNA for another (alpha 1) was not detected until after trophoblast outgrowth had begun, suggesting that its expression may be induced by contact with matrix. At E7.5, three of the temporally regulated integrins (alpha 1, apha 6A, alpha 7), all of which can form receptors for laminin, were detected only in the ectoplacental cone (differentiating trophoblast), and may thus play specific roles in trophoblast adhesion and/or differentiation. Because laminin expression is upregulated in decidualized uterine stroma in response to the implanting embryo, we examined trophoblast-laminin interactions, using laminin fragments and integrin antibodies to determine which integrin receptors were involved. Trophoblast cells attached and spread on both the E8 and P1' fragments of laminin; however, the P1' binding site was cryptic in intact laminin. Interaction with P1' was RGD- and alpha v beta 3-dependent, whereas outgrowth on E8 was RGD-independent and not inhibited by antibodies to the laminin receptor alpha 6 beta 1, suggesting that alpha 7 beta 1 is the major trophoblast integrin E8 receptor.(ABSTRACT TRUNCATED AT 400 WORDS)