How do migrating epithelia change direction?

摘要：动物一生都在建立和维持功能器官。为了构建一个器官，随着胚胎的发育，会发生多个步骤，既要制造该器官所需的所有不同类型的细胞，又要组织这些不同的细胞，以便它们能够共同工作来执行器官的功能。组织细胞的常见策略是通过协调细胞运动和形状变化。该项目旨在了解每种不同类型的细胞如何获得移动到正确位置并获得所需形状所需的信息。这个过程需要细胞相互识别，评估它们在发育组织中的当前位置，最后，使用来自它们的环境和/或它们的DNA蓝图中的信息，通过组织导航到需要它们的位置。为了了解细胞如何管理这种复杂的舞蹈，研究人员将研究一个例子，细胞组织起来创造一个器官样结构，发展成一个果蝇卵。蛋壳的形成需要一系列精确的细胞运动来保护发育中的胚胎。苍蝇卵巢将被培养，细胞运动将通过显微镜成像，使用遗传和抗体分析来识别细胞用于相互作用的特定蛋白质。这些研究将能够区分细胞运动的主要信息来源是来自内部程序还是来自外部环境线索。确定的蛋白质和机制将扩大细胞库的知识，可在动物门中观察到的许多不同类型的器官中创建有组织的结构。这项研究将为拉斯维加斯的内华达州大学的本科生和研究生提供必要的科学培训。他们将获得团队合作，批判性思维，数据管理的重要技能，以及进行实验室研究所需的技能。技术摘要：本提案的实验将研究迁移的细胞片层可以改变其迁移方向的机制。这项工作将侧重于果蝇的卵子发生，以利用先进的遗传操作工具和新技术对卵巢外植体中的细胞运动进行实时、延时成像。 基于以前的研究，两个模型的机制，诱导方向的变化将进行对比，这些模型是不相互排斥的。一种模型是每个细胞通过响应骨形态发生蛋白（BMP）形态发生梯度的调节基因表达的内在程序独立决定改变其方向。实验将测试特定的候选转录调节因子在新迁移的特定阶段开始时的要求。第二种模型是细胞对外来信号做出反应，重新定向它们的方向或以其他方式改变它们的迁移行为。该项目的这一方面跟进了已发表的报告，即BMP反应系统可能使用非转录机制来诱导细胞形状的变化，以及在这些细胞中调节另一种信号系统的初步数据。研究人员预测，内在的基因调控启动迁移反应的能力，而外在的信号引导细胞的迁移行为。这项工作将确定发育基因调控网络和细胞效应器之间的分子联系，这些细胞效应器创造了多细胞生物组织中所见的各种功能结构。除了这些研究活动外，研究人员还合作组织每月一次的科学咖啡馆（www.sciencecafes.org），为当地和区域科学家提供一个互动场所，与一般拉斯维加斯社区讨论当前的科学主题。

LAY ABSTRACT:Animals build and maintain functional organs throughout their lives. To build an organ, multiple steps occur as the embryo develops, both to make all the different types of cells needed for that organ, and to organize these different cells so that they can work together to perform the organ's function. A common strategy for organizing cells is through coordinated cellular movements and shape changes. This project aims to understand how each different kind of cell obtains the information it needs to move into the correct places and acquire the needed shape. This process requires that cells recognize each other, assess their current location in the developing tissue, and finally, use information from their environment and/or in their DNA blueprint to navigate through the tissue to the location where they are needed. To understand how cells manage this intricate dance, the investigator will study an example where cells organize to create an organlike structure that develops into a fruit fly egg. A series of precise cellular movements is needed to build the eggshell, which protects the developing embryo. Fly ovaries will be cultured and cell movements will be imaged through the microscope, using genetic and antibody assays to identify the specific proteins that cells use to interact with each other. These studies will be able to distinguish whether the major source of information for a cell's movements come from an internal program or from external environmental cues. The proteins and mechanisms identified will expand the knowledge of the cellular repertoire available to create organized structure in the many different types of organs observed across animal phyla. This research will provide essential scientific training for undergraduate and graduate students at the University of Nevada, Las Vegas. They will acquire important skills in teamwork, critical thinking, data management,as well as the needed skills to perform laboratory research.TECHNICAL ABSTRACT:The experiments of this proposal will examine the mechanisms by which a migrating sheet of cells can change its direction of migration. The work will focus on oogenesis of the fruit fly Drosophila melanogaster, to take advantage of sophisticated tools for genetic manipulations and new technologies for real-time, time-lapse imaging of cellular movements in ovary explants. Based on previous research, two models for the mechanisms that induce the change in direction will be contrasted; these models are not mutually exclusive. One model is that each cell decides independently to change its direction, through an intrinsic program of regulated gene expression in response to a bone morphogenetic protein (BMP) morphogen gradient. Experiments will test specific candidate transcriptional regulators for their requirements in the onset of specific phases of the new migration. The second model is that the cells respond to an extrinsic signal that reorients their direction or otherwise changes their migration behavior. This aspect of the project follows up on published reports that the BMP response system may use non-transcriptional mechanisms to induce changes in cell shape, as well as preliminary data that another signaling system is modulated in these cells. The investigator predicts that intrinsic gene regulation initiates the competence for a migration response, and that extrinsic signals orient the cells' migratory behaviors. This work will identify the molecular links between developmental gene regulatory networks and the cellular effectors that create the diverse array of functional architecture seen in tissues of multicellular organisms. In addition to these research activities, the investigator is collaboratively organizing a monthly Science Cafe (www.sciencecafes.org) to provide an interactive venue for local and regional scientists to discuss current scientific topics with the general Las Vegas community.