Making and breaking cell-cell contacts in development

上皮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。我们已经开发了一种遗传学上易于处理的体内模型来研究 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，从上皮细胞分离，迁移通过邻近组织，并粘附到新的 细胞在远处。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， 在体内经常成群移动。最近，已经清楚的是，细胞簇的传播是一种 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。人们对这种机制知之甚少， 在分层的过程中，单元集合体从它们最初的邻居中脱离。更少有人知道 细胞在到达最终目的地时如何建立新的连接。为了简洁起见，我们将此过程命名为 新层压 在这里，我们建议使用边界细胞来研究新层合的神秘过程： 绝佳的价钱在我们的第一个目标，我们建立在一个强大的基础上的初步数据描述的过程， 细胞从一个上皮细胞分离并迁移数小时后，连接到两种新的细胞类型： 卵母细胞和向心卵泡细胞。我们报告的过程中所需的基因鉴定，提供 分子机制的第一条线索在目标1中，我们建议将光生和热生结合起来， 这些方法已经彻底改变了神经科学和成像直接蛋白质的最先进方法， 活组织中的蛋白质相互作用，以研究这一重要的，但基本上没有研究过的过程。在目标2中， 建议研究卵母细胞内的细胞生物学过程和分子机制， 新层压工艺。在目标3中，我们建议使用同一套高度创新的方法来研究 在脱层过程中，边缘细胞最初是如何离开其原始上皮的。已经描述了 在前所未有的分辨率分层过程中，我们建议研究潜在的细胞和分子 机制等总体目标是建立一个概念模型，描述边界细胞如何整合 多个细胞外信号执行集体分层和新分层，并建立一个范例， 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.