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（由申请人提供）：该提案的目标是整合多个尺寸尺度的形态发生的生物力学，从亚细胞力的产生到指导发育中的青蛙胚胎收敛和延伸的宏观力和体组织特性。我们建议解决由内侧细胞嵌入的生物力学分析及其对组织变形的影响引起的一系列问题，并为未来形态发生的生物力学分析建立一个工具包。 极化突起产生的力是什么？它们如何转化为内侧细胞嵌入？这个问题涉及原肠胚形成过程中力的细胞起源。为了解决原肠胚形成过程中的这些力，我们将采用“力牵引”显微镜技术用于青蛙胚胎外植体，并将牵引力图像与这些外植体中外侧细胞嵌入期间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运动，我们需要了解机械背景，即发育中胚胎中组织的粘弹性特性以及它们与组织结构的关系。为了确定负责组织材料特性的 3D 组织结构的关键特征，我们建议测量背侧中胚层的整体机械特性，并通过组织学评估相关组织结构的特征。 最后，我们想要了解组织结构如何调节突出活动转化为组织伸展的体积力。为了测试关于细胞行为和组织延伸之间相互作用的假设，我们建议在改变突出活动、局部力产生或组织材料特性的处理后测量完整外植体的延伸力。 这项工作中建立的实验框架将通过提供具有可检验假设的形态发生的“具体细节”模型来补充正在进行的收敛和延伸分子调节因子的研究。我们的生物力学方法还将解决组织工程领域有关胚胎组织机械特性来源的基本问题，并提出胚胎如何构建复杂组织的相关案例研究。