Quantification of the mechanics of vertebrate body elongation

脊椎动物身体伸长力学的量化

• 批准号: 8837030
• 负责人: SCOTT A HOLLEY
• 金额: $ 31.59万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-15 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8837030
• 关键词: Adhesions; Architecture; Atomic Force Microscopy; Biological Assay; Biomechanics; Cadherins; Cell Differentiation process; Cell Proliferation; Cell-Cell Adhesion; Cells; Complement; Connective Tissue Cells; Coupling; Data; Defect; Development; Embryo; Embryonic Development; Engineering; Equilibrium; Extracellular Matrix; Fibronectins; Generations; Genes; Genetic; Health; Homeostasis; Image Analysis; Integrins; Knowledge; Life; Liquid substance; Measures; Mechanics; Mesoderm Cell; Morphology; Motion; Movement; Organogenesis; Paraxial Mesoderm; Pattern; Pattern Formation; Phase Transition; Phenotype; Process; Property; Regulation; Role; Sepharose; Solid; Spinal Cord; Stem cells; System; Systems Analysis; Tail; Testing; Three-Dimensional Imaging; Tissues; Traction; Transgenic Organisms; Zebrafish; biological systems; cell motility; driving force; fibrillogenesis; genetic analysis; imaging system; in vivo; man; melting; mutant; notochord; novel; physical property; prevent; progenitor; relating to nervous system; research study; resistant strain; vertebrate embryos

DESCRIPTION (provided by applicant): Man-made systems are assembled out of components with physical properties engineered to perform specific functions within the final assembly. By contrast, biological systems self- assemble, using genetic control to continuously regulate tissue biomechanics and tissue function throughout embryogenesis and organogenesis. Genetic analyses have revealed many of the underlying principles of pattern formation and cell differentiation during development. However, neither the biomechanics of development nor the genetic control of these biomechanics is well understood. The tailbud is the posterior leading edge of the growing vertebrate embryo and contains bipotential neural/mesodermal stem cells as well as spinal cord and mesodermal progenitors. This proposal focuses on the roles of cell-cell and cell-extracellular matrix (ECM) adhesion in defining tissue biomechanics in the extending tailbud. It is hypothesized that Fibronectn- dependent mechanical coupling between these tissues maintains parallel orientation of their posteriorly directed forces. This coupling increases the net posteriorly directed force. Within the posterior paraxial mesoderm, it is hypothesized that Fibronectin fibrillogenesi and remodeling drives tissue assembly. Tissue assembly requires integration of cell-cell and cell-ECM adhesion via Cadherin 2 which regulates Fibronectin matrix dynamics and produces a phase transition within the tissue from a viscoelastic fluid to a viscoelastic solid In Aim I-A, the lab will examine whether inter-tissue adhesion between the paraxial mesoderm and notochord promotes posterior elongation. In Aim I-B, the lab will quantify Fibronectin matrix dynamics in the paraxial mesoderm and test whether Fibronectin fibrillogenesis helps drive paraxial mesoderm elongation. In Aim II, the lab examines the roles of cadherin 2 and integrin ¿5 in regulating the transition in Fibronectin matrix and cell motion dynamics during the assembly of the paraxial mesoderm. In Aim III, the lab measures the contribution of these cell and tissue level processes to the generation of posteriorly directed force in the extending tailbud.

描述（由适用提供）：人造系统是由具有工程设计的组件组成的，该组件设计为在最终组装中执行特定功能。相比之下，生物系统自组成，使用遗传控制来连续调节整个胚胎发生和器官发生的组织生物力学和组织功能。遗传分析揭示了在发育过程中模式形成和细胞分化的许多基本原理。但是，发展的生物力学和这些生物力学的遗传控制都不良好。尾隙是生长脊椎动物胚胎的后端，并包含双性神经元/中胚层干细胞以及脊髓和中胚层祖细胞。该提案的重点是细胞细胞和细胞 - 细胞基质（ECM）粘附在定义延伸腹灌木中组织生物力学方面的作用。假设这些时序之间的纤连依赖性的机械耦合保持其向后定向力的平行方向。这种耦合增加了向后定向的净力。在近去近去中牙中心的内部，假设纤连蛋白原纤维蛋白原纤维蛋白和重塑驱动组织组装。 Tissue assembly requires integration of cell-cell and cell-ECM adhesive via Cadherin 2 which regulates Fibronectin matrix dynamics and produces a phase Transition within the tissue from a viscoelastic fluid to a viscoelastic solid In Aim I-A, the lab will examine whether inter-tissue adhesion between the paraxial mesoderm and notochord promotes posterior elongation.在AIM I-B中，该实验室将量化近似中胚层中的纤连蛋白基质动力学，并测试纤连蛋白原纤维蛋白原纤维生成是否有助于驱动近期中胚层的伸长。在AIM II中，该实验室检查了钙粘蛋白2和整联蛋白»5在调节纤连蛋白基质和细胞运动动力学过程中的跃迁中的作用。在AIM III中，实验室测量了这些细胞和组织水平过程对后部定向的产生的贡献 在延伸尾巴中武力。