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）：该提案的目的是整合从亚细胞生成力到宏观镜和块状组织特性的许多尺寸尺度的生物力学，以指导发育中的青蛙胚胎的收敛和扩展。我们建议解决一系列问题，这些问题是由中外侧细胞插入及其对组织变形的影响的生物力学分析引起的，并为未来的形态发生生物力学分析建立了工具包。 极化突起产生的力是什么？如何将其转化为中外侧细胞插入？这个问题涉及胃胃中力的细胞起源。为了解决这些在胃结构期间的力，我们将适应“力吸收”显微镜技术，可与青蛙胚胎外植体一起使用，并将牵引力的图像与这些epplatist剂中型外侧细胞插入过程中细胞突起的高分辨率成像结合在一起。 为了了解局部力的产生如何影响组织运动，我们需要了解机械环境，即发育中的胚胎中组织的粘弹性特性及其与组织结构的关系。为了确定负责组织材料特性的3D组织结构的关键特征，我们建议测量背膜的大量机械性能，并用组织学评估组织结构的特征。 最后，我们想了解组织结构如何调节爆发活性转化为组织扩展的大力。为了测试有关细胞行为与组织延伸之间相互作用的假设，我们建议测量在改变爆发活性，局部力量产生或组织材料特性的治疗后，完整的外植体的扩展力。 这项工作中建立的实验框架将通过提供可检验的假设的“螺母和螺栓”模型来补充对收敛和扩展分子调节剂的持续研究。我们的生物力学方法还将解决胚胎组织中机械性能来源的组织工程领域的基本问题，并提出了有关胚胎如何构建复杂组织的相关案例研究。