Xenopus embryonic cell adhesion to fibronectin: position-specific activation of RGD/synergy site-dependent migratory behavior at gastrulation.

Xenopus embryonic cell adhesion to fibronectin: position-specific activation of RGD/synergy site-dependent migratory behavior at gastrulation.
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DOI:
10.1083/jcb.134.1.227
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发表时间:
1996-07
影响因子:
7.8
通讯作者:
DeSimone, DW
DeSimone, DW
中科院分区:
生物学1区
文献类型:
--
作者:
Ramos, JW;DeSimone, DW

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在非洲爪蟾原肠胚形成期间,胚胎的基本身体平面是通过囊胚的边缘区细胞移动到囊胚腔中而产生的。该形态发生过程涉及细胞粘附到细胞外基质蛋白纤连蛋白(FN)。在体外使用FN融合蛋白底物分析了退化边缘区(IMZ)细胞附着和迁移所需的FN区域。IMZ细胞与FN的附着由位于Hep II结构域的III-10型重复中的Arg-Gly-Asp(RGD)序列和III-13型重复中的Pro-Pro-Arg-Arg-Ala-Arg(PPRRAR)序列介导。IMZ细胞在含有位于III-9型重复序列中的RGD和协同位点序列Pro-Pro-Ser-Arg-Asn(PPSRN)的融合蛋白上持续扩散和迁移。协同位点的细胞识别在早期胚胎中受到位置调节。在原肠胚形成期间,IMZ细胞将在FN上扩散和迁移,而假定的前退化中胚层、植物极内胚层和动物帽外胚层则不会。然而,当用中胚层诱导因子激活素A处理时,动物帽外胚层细胞获得在RGD/协同区域上扩散和迁移的能力。这些数据表明,中胚层诱导激活了体内FN协同位点的位置特异性识别。此外,我们证明了该网站的功能的重要性,使用单克隆抗体,阻止协同区域依赖的细胞扩散和迁移FN。当将该抗体注射到囊胚腔中时,正常的IMZ运动受到干扰,表明IMZ细胞与协同区域的相互作用是正常原肠胚形成所需的。
During Xenopus laevis gastrulation, the basic body plan of the embryo is generated by movement of the marginal zone cells of the blastula into the blastocoel cavity. This morphogenetic process involves cell adhesion to the extracellular matrix protein fibronectin (FN). Regions of FN required for the attachment and migration of involuting marginal zone (IMZ) cells were analyzed in vitro using FN fusion protein substrates. IMZ cell attachment to FN is mediated by the Arg-Gly-Asp (RGD) sequence located in the type III-10 repeat and by the Pro-Pro-Arg- Arg-Ala-Arg (PPRRAR) sequence in the type III-13 repeat of the Hep II domain. IMZ cells spread and migrate persistently on fusion proteins containing both the RGD and synergy site sequence Pro-Pro-Ser-Arg-Asn (PPSRN) located in the type III-9 repeat. Cell recognition of the synergy site is positionally regulated in the early embryo. During gastrulation, IMZ cells will spread and migrate on FN whereas presumptive pre-involuting mesoderm, vegetal pole endoderm, and animal cap ectoderm will not. However, animal cap ectoderm cells acquire the ability to spread and migrate on the RGD/synergy region when treated with the mesoderm inducing factor activin-A. These data suggest that mesoderm induction activates the position-specific recognition of the synergy site of FN in vivo. Moreover, we demonstrate the functional importance of this site using a monoclonal antibody that blocks synergy region-dependent cell spreading and migration on FN. Normal IMZ movement is perturbed when this antibody is injected into the blastocoel cavity indicating that IMZ cell interaction with the synergy region is required for normal gastrulation.
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