Mechanisms of cell coordination in epithelial morphogenesis analyzed by quantitative 3D imaging

通过定量 3D 成像分析上皮形态发生中的细胞协调机制

• 批准号: 418438-2013
• 负责人: FernandezGonzalez, Rodrigo
• 金额: $ 3.5万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=650663
• 关键词: Mechanisms; cell; coordination; epithelial; morphogenesis

During embryonic development and tissue repair, cells move over long distances and undergo dramatic changes in shape, and in so doing, they push, pull and deform their neighbors. Therefore, an exquisite degree of coordination is necessary to preserve the integrity of tissues when cells move or generate physical forces. Although the main molecular players involved in force generation are known, the mechanisms by which cells coordinate their behaviors remain a mystery, mainly because it is difficult to establish the initial events that trigger cells to act together. Notably, wound healing in embryos of many different species is driven by the coordinated generation of force by the cells adjacent to the wound. In wound healing one can clearly establish and deliver at will the signal that induces cell coordination (the wound), making it an ideal system to investigate the mechanisms of coordinated force generation. **** We propose to investigate the physical and molecular mechanisms of cell coordination using wound repair in Drosophila embryos as a model system. We will do these through 3 projects in which we will take advantage of the powerful live imaging and genetic tools available in Drosophila, and of our previous experience developing quantitative image analysis tools and biophysical methods to locally manipulate forces in embryos. This research program will be pioneer in Canada in the establishment and application of biophysical methods, including magnetic tweezers or laser ablation, for their use in living organisms, as well as in the creation of new of tools for high-throughput, microscopy-based screening that will be of use to other researchers. Completing these aims will also serve the purpose of providing 3 Ph.D. students and several summer students with training in the areas of image analysis, biophysics, and cell and developmental biology. Trainees with this multidisciplinary background are currently in high demand in Canada, both in academia and in industry (biotech, pharmaceutical, software engineering). ********

在胚胎发育和组织修复过程中，细胞移动了很长的距离，并且在形状上发生了巨大的变化，在这个过程中，它们推动、拉动并使它们的邻居变形。因此，当细胞移动或产生物理力时，需要高度的协调来保持组织的完整性。虽然参与力产生的主要分子是已知的，但细胞协调其行为的机制仍然是一个谜，主要是因为很难确定触发细胞共同行动的初始事件。值得注意的是，在许多不同物种的胚胎中，伤口愈合是由靠近伤口的细胞协调产生的力驱动的。在伤口愈合中，人们可以清晰地建立并随意传递诱导细胞协调（伤口）的信号，使其成为研究协调力产生机制的理想系统。****我们建议以果蝇胚胎伤口修复为模型系统来研究细胞协调的物理和分子机制。我们将通过3个项目来实现这些，在这些项目中，我们将利用强大的实时成像和果蝇遗传工具，以及我们以前开发定量图像分析工具和生物物理方法的经验来局部操纵胚胎中的力。该研究项目将成为加拿大在生物物理方法的建立和应用方面的先驱，包括磁镊子或激光消融，用于生物有机体，以及为其他研究人员提供高通量、基于显微镜的筛选新工具的创建。完成这些目标还将为3名博士生和几名暑期学生提供图像分析、生物物理学、细胞和发育生物学等领域的培训。具有这种多学科背景的学员目前在加拿大学术界和工业界（生物技术、制药、软件工程）都有很高的需求。* * * * * * * *