A polarized actin cytoskeleton and its role in cortical patterning in early Drosophila embryos

皮质区，即顶区、亚尖区、侧区和基底区，是上皮细胞的特征。虽然一些与质膜整合或结合的蛋白质是均匀分布的，但另一些蛋白质仅限于特定的所谓皮质区。皮质结构域是上皮细胞的一个决定性特征，因为它们为分化后的重要功能分子的定位提供了模板。除了它们在发育和分化中的重要性外，作为上皮-间充质转化的一部分，皮质图案的形成、改变或丧失也是肿瘤发生中的重要步骤，因此具有重要的医学意义。尽管先前在各种实验系统中已经确定了蛋白质和蛋白质复合体最初分离和维持特定皮质区域分布的多种机制，但缺乏一个结论性和统一的观点。在这里，我们分析了果蝇早期胚胎发育过程中亚顶域的出现。在拟议的项目中，我们将测试新的模型，即极化的皮质肌动蛋白在从合胞到细胞发育的转变过程中导致亚顶端决定因素的限制。具体地说，我们将开发标记F-肌动蛋白(+)末端的分析方法，皮质肌动蛋白的可视化，并解决Forin Dia、运动蛋白Myo II和微管运动蛋白-1的功能。

Cortical domains, i. e. apical, sub-apical, lateral and basal domains, are a characteristic feature of epithelial cells. While some proteins integrated or associated with the plasma membrane are uniformly distributed, others are restricted to specific so-called cortical domains. Cortical domains are an defining feature of epithelial cells, since they provide the template for localization of functionally important molecules after differentiation. Beside their importance in development and differentiation, the formation, change or loss of cortical patterning as part of an epithelial-mesenchymal transition are important steps in tumorigenesis and are thus of great medical relevance. Although multiple mechanism for the initial segregation and maintenance of the distribution of proteins and protein complexes to specific cortical domains have been previously identified in a variety of experimental systems, a conclusive and unifying view is missing. Here we analyse the emergence of the sub apical domain during early Drosophila embryogenesis. In the proposed project, we will test the novel model that polarised cortical actin leads to restriction of sub apical determinants during the transition from syncytial to cellular development. Specifically we will develop assays for labelling the (+)-ends of F-actin, visualisation of cortical actin and address the function of the formin Dia, the motor protein Myo II and the microtubule motor Kinesin-1.