Making and breaking cell-cell contacts in development

上皮细胞动力学在胚胎发育和伤口愈合过程中至关重要，并被癌症劫持。 细胞在转移过程中的作用。我们已经开发了一种遗传上容易处理的活体模型来研究 一组上皮细胞，果蝇卵巢的边缘细胞，表现出动态的细胞行为包括 获得运动性，脱离上皮，在邻近组织中迁移，并附着于新的 在遥远地点的细胞。虽然大多数关于细胞运动的研究都集中在体外的单个细胞上，但细胞 经常在活体内成群移动。最近有一点变得很清楚，细胞簇的扩散是一种 癌症转移的常见来源。大多数关于个体和集体细胞运动性的研究都集中在 细胞从一个地方迁移到另一个地方的中间步骤。人们对其机制知之甚少。 在分层的过程中，细胞集体脱离了它们最初的邻居。人们对此知之甚少 细胞到达最终目的地后如何建立新的连接。简而言之，我们将这个过程命名为 新层析。 在这里，我们建议使用边界细胞来研究新分层的神秘过程：依附于一个新的 地点。在我们的第一个目标中，我们建立在描述边界的过程的初步数据的坚实基础上 细胞从一种上皮细胞分离并迁移几个小时后，连接成两种新的细胞类型： 卵母细胞和向心性滤泡细胞。我们报告了这一过程所需基因的鉴定，提供了 分子机制的第一个线索。在目标1中，我们建议将光生和热生结合起来 已经彻底改变了神经科学和最先进的直接蛋白质成像方法的方法- 活体组织中的蛋白质相互作用，以研究这一基本但基本上未被研究的过程。在目标2中，我们 建议研究卵母细胞内的细胞生物学过程和分子机制 新的分层过程。在目标3中，我们建议使用相同的一套高度创新的方法来研究 在分层的过程中，边缘细胞最初是如何离开它们起源的上皮的。在描述了 分层过程以前所未有的分辨率，我们建议研究潜在的细胞和分子 机械装置。首要目标是构建描述边界单元如何集成的概念模型 多个细胞外信号来执行集体分层和新分层，并建立 对这些关键的动态细胞行为的研究。

Epithelial dynamics are critical during embryonic development and wound healing and are hijacked by cancer cells during the process of metastasis. We have developed a genetically tractable in vivo model to study a group of epithelial cells, the border cells of the Drosophila ovary, which exhibit dynamic cell behaviors including acquiring motility, detaching from an epithelium, migrating through neighboring tissue, and adhering to new cells at a distant site. While most studies of cell movements have focused on individual cells in vitro, cells frequently move in groups in vivo. Recently it has become clear that dissemination of clusters of cells is a common source of metastases in cancer. Most studies of both individual and collective cell motility focus on the intermediate step as cells migrate from one place to another. Little is known of the mechanisms by which cell collectives break away from their initial neighbors in the process of delamination. Even less is known about how cells make new connections upon arrival at their ultimate destination. To be concise we name this process neolamination. Here we propose to use the border cells to study the mysterious process of neolamination: attaching to a new site. In our first aim we build on a strong foundation of preliminary data describing the process by which border cells, after detaching from one epithelium and migrating for several hours, connect up to two new cell types: the oocyte and centripetal follicle cells. We report the identification of genes required for the process, providing the first clues to the molecular mechanism. In Aim 1, we propose to combine opto- and thermo-genetic approaches that have revolutionized neuroscience and state-of-the-art methods for imaging direct protein- protein interactions in living tissue, to study this essential, yet essentially unstudied, process. In Aim 2, we propose to study the cell biological processes and molecular mechanisms operating within the oocyte during the neolamination process. In Aim 3, we propose to use the same set of highly innovative approaches to study how border cells initially leave their epithelium of origin, in the process of delamination. Having described the delamination process at unprecedented resolution, we propose to study the underlying cellular and molecular mechanisms. The overarching goal is to build a conceptual model describing how the border cells integrate multiple extracellular signals to execute collective delamination and neolamination and establish a paradigm for the study of these critical dynamic cellular behaviors.