The Role of Mechanical Interactions in Tissue Formation and Body Axis Specification

机械相互作用在组织形成和身体轴规范中的作用

• 批准号: 1463572
• 负责人: Eva-Maria Collins
• 金额: $ 41.46万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1463572&HistoricalAwards=false
• 关键词: Role; Mechanical; Interactions; Tissue; Formation

Despite their remarkable diversity, all animals begin as a single, fertilized egg. How patterns are established from an initially near uniform system, the egg, is a fundamental question in biology. Mechanical interactions between cells and their environment are thought to play an important role in tissue and axis formation, but this has been difficult to dissect experimentally because of the complexity of developing embryos. The award will investigate the role of mechanical forces in the formation of body form of the Hydra from a solution of separated cells. How the tension at the cell surface and the stiffness of layers of tissue fibers that the cells secrete change how the animal structure develops also will be measured. This award supports fundamental research aimed at studying a simple animal that can regenerate its body after dissociation into individual cells. The core mechanical mechanisms of cell-cell interactions during body plan development are universal during early development. Understanding how these mechanisms work in a simple organism will lead to insight into these mechanisms in more complex beings. This research may reveal general guiding principles for tissue assembly and organ formation and thus has implications for medicine in the context of engineering tissues and organs for transplantation. Understanding how an organism can emerge from an aggregation of cells sparks human imagination. Therefore this project will offer exciting research opportunities for undergraduate and graduate students. The interdisciplinary nature of the project requires the application of tools from physics, biology, engineering, and computer science, and thus will enable students from diverse backgrounds to make significant contributions.It is experimentally challenging to dissect the mechanical interactions involved in animal development. A novel system which promises to allow such a dissection is the freshwater polyp Hydra, which self-organizes and regenerates after dissociation into a suspension of single cells. Because of this remarkable ability and its structural simplicity, regenerating Hydra aggregates are fully accessible to quantitative measurements and controlled perturbations while providing an in vivo environment that makes the measurements meaningful. This research will elucidate how tissue formation occurs from a cell suspension and determine the mechanisms that lead to body axis specification. For both processes, the research team will apply a multiscale approach from the molecular to the organismal level and test the importance of mechanical interactions using physical measurements, chemical manipulations, visualization of gene expression using transgenic animals and immunohistochemistry, and fluorescent time-lapse microscopy. This study will provide insight into how macroscopic organism-level patterning emerges from interactions on the cellular level.

尽管它们有着显著的多样性，但所有的动物开始都是从一个受精卵开始的。模式是如何从一个最初近乎均匀的系统--鸡蛋--建立起来的，这是生物学中的一个基本问题。细胞与其环境之间的机械相互作用被认为在组织和轴的形成中起着重要作用，但由于发育胚胎的复杂性，这在实验上很难解剖。该奖项将研究机械力在从分离的细胞溶液形成水螅体形式中的作用。细胞表面的张力和细胞分泌的组织纤维层的硬度如何改变动物结构的发育也将被测量。 该奖项支持旨在研究一种简单动物的基础研究，这种动物可以在分解成单个细胞后再生其身体。在身体平面发育过程中细胞-细胞相互作用的核心力学机制在早期发育过程中是普遍的。 了解这些机制如何在一个简单的有机体中工作，将有助于深入了解这些机制在更复杂的生物。这项研究可能揭示组织组装和器官形成的一般指导原则，因此对工程组织和器官移植的医学有影响。了解有机体如何从细胞聚集体中产生激发了人类的想象力。因此，该项目将为本科生和研究生提供令人兴奋的研究机会。该项目的跨学科性质需要应用物理学，生物学，工程学和计算机科学的工具，因此将使来自不同背景的学生做出重大贡献。它是具有实验挑战性的解剖动物发育中涉及的机械相互作用。一个新的系统，承诺允许这样的解剖是淡水息肉水螅，自我组织和再生后，解离成一个悬浮的单细胞。由于这种非凡的能力及其结构简单性，再生水螅聚集体完全可用于定量测量和受控扰动，同时提供使测量有意义的体内环境。这项研究将阐明如何从细胞悬浮液中形成组织，并确定导致体轴规格的机制。对于这两个过程，研究小组将采用从分子到生物体水平的多尺度方法，并使用物理测量，化学操作，使用转基因动物和免疫组织化学的基因表达可视化以及荧光延时显微镜来测试机械相互作用的重要性。这项研究将提供深入了解宏观生物体水平的模式如何从细胞水平上的相互作用中出现。