Grawe F, Wodarz A, Lee B, Knust E, Skaer H
Institut für Entwicklungsbiologie, Universität zu Köln, Germany.
Development. 1996 Mar;122(3):951-9. doi: 10.1242/dev.122.3.951.
Morphogenetic movements of epithelia during development underlie the normal elaboration of the final body plan. The tissue integrity critical for these movements is conferred by anchorage of the cytoskeleton by adherens junctions, initially spot and later belt-like, zonular structures, which encircle the apical side of the cell. Loss-of-function mutations in the Drosophila genes crumbs and stardust lead to the loss of cell polarity in most ectodermally derived epithelia, followed in some, such as the epidermis, by extensive apoptosis. Here we show that both mutants fail to establish proper zonulae adherentes in the epidermis. Our results suggest that the two genes are involved in different aspects of this process. Further, they are compatible with the hypothesis that crumbs delimits the apical border, where the zonula adherens usually forms and where Crumbs protein is normally most abundant. In contrast, stardust seems to be required at an earlier stage for the assembly of the spot adherence junctions. In both mutants, the defect observed at the ultrastructural level are preceded by a misdistribution of Armadillo and DE-cadherin, the homologues of beta-catenin and E-cadherin, respectively, which are two constituents of the vertebrate adherens junctions. Strikingly, expansion of the apical membrane domain in epidermal cells by overexpression of crumbs also abolishes the formation of adherens junctions and results in the disruption of tissue integrity, but without loss of membrane polarity. This result supports the view that membrane polarity is independent of the formation of adherens junctions in epidermal cells.
上皮细胞在发育过程中的形态发生运动是最终身体结构正常形成的基础。这些运动所必需的组织完整性是由细胞骨架通过黏着连接锚定赋予的，黏着连接最初是点状的，后来是带状的、小带样结构，环绕着细胞的顶端。果蝇基因crumbs和stardust的功能丧失突变导致大多数外胚层来源的上皮细胞失去细胞极性，在某些组织中，如表皮，随后会发生广泛的细胞凋亡。在这里，我们表明这两种突变体在表皮中都无法建立正常的黏着小带。我们的结果表明，这两个基因参与了这个过程的不同方面。此外，它们与以下假设相符：crumbs界定了顶端边界，黏着小带通常在此形成，且Crumbs蛋白通常在此最为丰富。相比之下，stardust似乎在更早的阶段是点状黏附连接组装所必需的。在这两种突变体中，在超微结构水平观察到的缺陷之前，分别是犰狳蛋白和DE-钙黏蛋白（分别是β-连环蛋白和E-钙黏蛋白的同源物）的分布错误，它们是脊椎动物黏着连接的两个组成部分。令人惊讶的是，通过过表达crumbs使表皮细胞顶端膜结构域扩张也会消除黏着连接的形成并导致组织完整性的破坏，但不会导致膜极性的丧失。这一结果支持了膜极性独立于表皮细胞中黏着连接形成的观点。
