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

极化肌动蛋白细胞骨架及其在早期果蝇胚胎皮质模式中的作用

• 批准号: 436484648
• 负责人: Professor Dr. Jörg Großhans
• 金额: --
• 依托单位: Arbeitsgruppe Entwicklungsgenetik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/436484648?language=en
• 关键词: polarized; actin; cytoskeleton; its; role

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.

皮质区，i. e.顶端、亚顶端、侧面和基底区域是上皮细胞的特征。虽然与质膜整合或结合的一些蛋白质是均匀分布的，但其他蛋白质仅限于特定的所谓皮质结构域。皮质结构域是上皮细胞的定义特征，因为它们为分化后功能重要分子的定位提供模板。除了它们在发育和分化中的重要性之外，作为上皮-间充质转化的一部分的皮质图案的形成、改变或丧失是肿瘤发生中的重要步骤，因此具有很大的医学相关性。虽然先前在各种实验系统中已经确定了蛋白质和蛋白质复合物分布到特定皮质域的初始分离和维持的多种机制，但缺乏结论性和统一的观点。在这里，我们分析了出现在早期果蝇胚胎发育的亚顶端域。在拟议的项目中，我们将测试新的模型，极化皮质肌动蛋白导致限制次顶端决定因素从合胞体过渡到细胞发育。具体来说，我们将开发用于标记F-肌动蛋白的（+）-末端，皮质肌动蛋白的可视化的测定，并解决了Dia，马达蛋白Myo II和微管马达驱动蛋白-1的功能。