How do migrating epithelia change direction?

迁移上皮如何改变方向？

基本信息

批准号：
1355091
负责人：
Laurel Raftery
金额：
$ 51.45万
依托单位：
University of Nevada Las Vegas
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2019-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1355091&HistoricalAwards=false
关键词：
How do migrating epithelia change

项目摘要

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.

摘要：动物一生都建立和维护功能器官。为了构建器官，随着胚胎的发展而发生多个步骤，既可以使该器官所需的所有不同类型的单元格进行，又可以组织这些不同的细胞，以便它们可以一起工作以执行器官的功能。组织细胞的常见策略是通过协调的细胞运动和形状变化。该项目旨在了解每种不同类型的单元格如何获得进入正确位置并获得所需形状所需的信息。这个过程要求细胞互相识别，评估其当前位置在发育中的组织中，最后使用来自其环境和/或DNA蓝图中的信息，将组织导航到需要的位置。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示例，其中细胞会在其中创建一个有细胞的结构，从而发展成果蝇卵。需要一系列精确的细胞运动来构建蛋壳，从而保护发育中的胚胎。将使用遗传和抗体测定法培养卵巢，并通过显微镜成像细胞运动，以识别细胞用来相互相互作用的特定蛋白质。这些研究将能够区分单元运动的主要信息来源是内部程序还是来自外部环境提示。所确定的蛋白质和机制将扩大可用于在动物门上观察到的许多不同类型的器官中创建有组织结构的细胞库的知识。这项研究将为内华达大学拉斯维加斯大学的本科生和研究生提供基本的科学培训。他们将获得团队合作，批判性思维，数据管理以及执行实验室研究所需的技能的重要技能。技术摘要：该提案的实验将研究迁移的细胞表可以改变其迁移方向的机制。这项工作将着重于果蝇果蝇的卵子发生，以利用遗传操作的复杂工具和新技术，用于实时，延迟的卵巢外植体细胞运动的成像。基于先前的研究，将对比诱导方向变化的机制的两个模型。这些模型不是互斥的。一个模型是，每个细胞都通过响应骨形态发生蛋白（BMP）形态梯度的固有程序来独立决定改变其方向。实验将在新迁移的特定阶段开始测试特定的候选转录调节器的要求。第二个模型是细胞对外在信号的响应，该信号重新定向其方向或以其他方式改变其迁移行为。该项目的这一方面遵循已发表的报告，即BMP响应系统可以使用非转录机制来诱导细胞形状变化，以及初步数据，即在这些单元中调制了另一个信号系统。研究者预测，内在基因调节会启动迁移反应的能力，并且外部信号将细胞的迁移行为定向。这项工作将确定发育基因调节网络与细胞效应子之间的分子联系，这些效应产生了在多细胞生物组织中看到的各种功能结构。除了这些研究活动外，研究人员还合作组织了一个每月的科学咖啡馆（www.sciencecafes.org），为地方和地区科学家提供互动场所，以与一般的拉斯维加斯社区讨论当前的科学话题。