Regulation of C-cadherin function during activin induced morphogenesis of Xenopus animal caps.
Regulation of C-cadherin function during activin induced morphogenesis of Xenopus animal caps.
复制标题
DOI：
10.1083/jcb.126.2.519
复制
发表时间：
1994-07
期刊：
影响因子：
--
通讯作者：
Gumbiner BM
中科院分区：
文献类型：
--
作者：
Brieher WM;Gumbiner BM
用激活素处理非洲爪蟾动物极组织导致中胚层细胞类型的诱导和组织的显著伸长。参与延伸的形态发生运动似乎与正常原肠胚形成中的运动相似，这是由细胞重排和细胞插入驱动的。我们已经使用这个系统来探索在形态发生过程中细胞-细胞粘附和钙粘蛋白功能的潜在调节。定量卵裂球聚集试验显示激活素诱导降低了卵裂球之间的钙依赖性粘附。激活素诱导的卵裂球形成更小的聚集体，并且与未诱导的卵裂球相比，更大比例的群体保持为单细胞。聚集是由C-cadherin介导的，因为C-cadherin在聚集试验期间存在于卵裂球中，并且针对C-cadherin的单克隆抗体抑制卵裂球的钙依赖性聚集。直到检测完成后才能检测到E-钙粘蛋白，因此无法解释诱导和未诱导卵裂球之间的粘附差异。使用稳定表达C-钙粘蛋白的L细胞（LC细胞）来证明C-钙粘蛋白活性在激活素诱导后特异性改变。激活素诱导的卵裂球比未诱导的卵裂球结合更少的LC细胞。不表达C-cadherin的L细胞不粘附于卵裂球。在C-钙粘蛋白介导的粘附的变化发生没有检测到的变化，在稳态水平的C-钙粘蛋白或C-钙粘蛋白的量存在于细胞表面上。C-钙粘蛋白及其相关的连环蛋白的免疫沉淀显示，C-钙粘蛋白和连环蛋白的比例没有改变激活素诱导。这些结果表明，激活素降低了卵裂球表面上现有C-钙粘蛋白分子的粘附功能，并表明钙粘蛋白介导的细胞-细胞粘附的降低与形态发生运动的增加相关。
Treatment of Xenopus animal pole tissue with activin results in the induction of mesodermal cell types and a dramatic elongation of the tissue. The morphogenetic movements involved in the elongation appear similar to those in normal gastrulation, which is driven by cell rearrangement and cell intercalations. We have used this system to explore the potential regulation of cell-cell adhesion and cadherin function during morphogenesis. Quantitative blastomere aggregation assays revealed that activin induction reduced the calcium-dependent adhesion between blastomeres. Activin-induced blastomeres formed smaller aggregates, and a greater proportion of the population remained as single cells compared to uninduced blastomeres. The aggregation was mediated by C-cadherin because C-cadherin was present in the blastomeres during the aggregation assay, and monoclonal antibodies against C-cadherin inhibited the calcium-dependent aggregation of blastomeres. E-cadherin was not detectable until after the completion of the assay and, therefore, does not explain the adhesive differences between induced and uninduced blastomeres. L cells stably expressing C- cadherin (LC cells) were used to demonstrate that C-cadherin activity was specifically altered after activin induction. Blastomeres induced with activin bound fewer LC cells than uninduced blastomers. L cells not expressing C-cadherin did not adhere to blastomeres. The changes in C-cadherin-mediated adhesion occurred without detectable changes in the steady-state levels of C-cadherin or the amount of C-cadherin present on the surface of the cell. Immunoprecipitation of C-cadherin and its associated catenins revealed that the ratio of C-cadherin and the catenins was not altered by activin induction. These results demonstrate that activin decreases the adhesive function of existing C- cadherin molecules on the surface of blastomeres and suggest that decreased cadherin mediated cell-cell adhesion is associated with increased morphogenetic movement.