The biomechanics of morphogenesis in the frog

青蛙形态发生的生物力学

• 批准号: 6871728
• 负责人: LANCE A. DAVIDSON
• 金额: $ 32.42万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6871728
• 关键词: Xenopus; bioimaging /biomedical imaging; biomechanics; cell cell interaction; cellular polarity; embryogenesis; histogenesis; mesoderm; microscopy; tissue support frame; vertebrate embryology; viscosity

DESCRIPTION (provided by applicant): The goal of this proposal is to integrate the biomechanics of morphogenesis across a number of size-scales from subcellular generation of forces to the macroscopic forces and bulk tissue properties that guide convergence and extension in the developing frog embryo. We propose to address a series of questions that arise from a biomechanical analysis of mediolateral cell intercalation and its effects on tissue deformation and establish a toolkit for future biomechanical analyses of morphogenesis. What are the forces generated by polarized protrusions and how are they converted into mediolateral cell intercalation? This question concerns the cellular origin of force during gastrulation. To resolve these forces during gastrulation we will adapt "force-traction" microscopy techniques for use with frog embryo explants and combine images of traction-forces with high resolution imaging of cell protrusions during mediolateral cell intercalation in these explants. In order to understand how local force generation effects tissue movement we need to understand the mechanical context, i.e. the viscoelastic properties of tissues in the developing embryo and how they relate to tissue architecture. To identify key features of the 3D tissue architecture that are responsible for tissue material properties we propose to measure bulk mechanical properties of the dorsal mesoderm and assess with histology the features of the tissue architecture that are relevant. Lastly, we want to understand how the tissue architecture modulates conversion of protrusive activity into the bulk forces of tissue extension. In order to test hypotheses on the interactions between cell behaviors and tissue extension we propose to measure the force of extension of intact explants after treatments that alter protrusive activity, local force generation, or tissue material properties. The experimental framework established in this work will complement ongoing studies of the molecular regulators of convergence and extension by providing "nuts-and-bolts" models of morphogenesis with testable hypotheses. Our biomechanical approach will also address basic questions from the field of tissue engineering on the source of mechanical properties in embryonic tissues and presents a relevant case study of how embryos build a complex tissue.

描述(申请人提供)：这项建议的目标是将形态发生的生物力学整合到多个大小的尺度上，从亚细胞生成的力到引导青蛙胚胎发育中汇聚和延伸的宏观力和整体组织属性。我们建议解决由生物力学分析产生的一系列问题，内侧细胞插入及其对组织变形的影响，并为未来形态发生的生物力学分析建立一个工具箱。 极化突起产生的力是什么，它们是如何转化为内侧细胞嵌入的？这个问题涉及原肠形成过程中的细胞内力来源。为了解决原肠形成过程中的这些力，我们将采用用于青蛙胚胎外植体的“力牵引”显微镜技术，并将牵引力图像与这些外植体中外侧细胞嵌入过程中细胞突起的高分辨率成像相结合。 为了了解局部力的产生如何影响组织的运动，我们需要了解力学背景，即发育中的胚胎组织的粘弹性特性以及它们与组织结构的关系。为了确定决定组织材料特性的3D组织结构的关键特征，我们建议测量背侧中胚层的整体力学特性，并与组织学评估相关的组织结构特征。 最后，我们想了解组织结构是如何将突起活动转化为组织伸展的整体力量的。为了测试细胞行为和组织伸展之间相互作用的假设，我们建议测量在改变突起活动、局部力产生或组织材料属性的处理后完整外植体的伸长力。 这项工作中建立的实验框架将补充正在进行的关于收敛和延伸的分子调节器的研究，提供具有可检验的假说的形态发生的“螺母和螺栓”模型。我们的生物力学方法还将解决组织工程领域关于胚胎组织机械特性来源的基本问题，并提供一个关于胚胎如何构建复杂组织的相关案例研究。