Cox R T, Kirkpatrick C, Peifer M
Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, 27599-3280, USA.
J Cell Biol. 1996 Jul;134(1):133-48. doi: 10.1083/jcb.134.1.133.
Morphological and biochemical analyses have identified a set of proteins which together form a structure known as the adherens junction. Elegant experiments in tissue culture support the idea that adherens junctions play a key role in cell-cell adhesion and in organizing cells into epithelia. During normal embryonic development, cells quickly organize epithelia; these epithelial cells participate in many of the key morphogenetic movements of gastrulation. This prompted the hypothesis that adherens junctions ought to be critical for normal embryonic development. Drosophila Armadillo, the homologue of vertebrate beta-catenin, is a core component of the adherens junction protein complex and has been hypothesized to be essential for adherens junction function in vivo. We have used an intermediate mutant allele of armadillo, armadilloXP33, to test these hypotheses in Drosophila embryos. Adherens junctions cannot assemble in the absence of Armadillo, leading to dramatic defects in cell-cell adhesion. The epithelial cells of the embryo lose adhesion to each other, round up, and apparently become mesenchymal. Mutant cells also lose their normal cell polarity. These disruptions in the integrity of epithelia block the appropriate morphogenetic movements of gastrulation. These results provide the first demonstration of the effect of loss of adherens junctions on Drosophila embryonic development.
形态学和生化分析已经鉴定出一组蛋白质,它们共同形成一种被称为黏着连接的结构。组织培养中的精妙实验支持了这样一种观点,即黏着连接在细胞间黏附以及将细胞组织成上皮细胞层的过程中发挥着关键作用。在正常胚胎发育过程中,细胞迅速组织形成上皮细胞层;这些上皮细胞参与了原肠胚形成过程中的许多关键形态发生运动。这引发了一种假说,即黏着连接对于正常胚胎发育至关重要。果蝇中的犰狳蛋白(Armadillo)是脊椎动物β-连环蛋白的同源物,是黏着连接蛋白复合物的核心成分,并且据推测对于黏着连接在体内的功能至关重要。我们利用犰狳蛋白的一个中间突变等位基因armadilloXP33,在果蝇胚胎中检验这些假说。在没有犰狳蛋白的情况下,黏着连接无法组装,导致细胞间黏附出现严重缺陷。胚胎的上皮细胞彼此失去黏附,变圆,并且明显变成间充质细胞。突变细胞也失去了正常的细胞极性。上皮细胞层完整性的这些破坏阻碍了原肠胚形成过程中适当的形态发生运动。这些结果首次证明了黏着连接缺失对果蝇胚胎发育的影响。