Quantification of the mechanics of vertebrate body elongation

脊椎动物身体伸长力学的量化

• 批准号: 9043110
• 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/9043110
• 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; knock-down; 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（由申请人提供）：人造系统是由具有设计的物理特性的组件组装而成，以在最终组件中执行特定功能。 相比之下，生物系统自组装，使用遗传控制在整个胚胎发生和器官发生中连续调节组织生物力学和组织功能。 遗传分析揭示了许多基本原则的模式形成和细胞分化过程中的发展。然而，无论是发育的生物力学还是这些生物力学的遗传控制都没有得到很好的理解。 尾芽是脊椎动物胚胎生长的后前缘，含有双能神经/中胚层干细胞以及脊髓和中胚层祖细胞。 该提案重点关注细胞与细胞和细胞与细胞外基质（ECM）粘附在定义延伸尾芽中的组织生物力学方面的作用。 假设这些组织之间的纤连蛋白依赖性机械偶联保持其向后定向力的平行取向。 这种耦合增加了净后向力。在后近轴中胚层内，假设纤连蛋白原纤维发生和重塑驱动组织组装。组织组装需要通过钙粘蛋白2整合细胞-细胞和细胞-ECM粘附，钙粘蛋白2调节纤连蛋白基质动力学并在组织内产生从粘弹性流体到粘弹性固体的相变 在目标I-A中，实验室将检查近轴中胚层和脊索之间的组织间粘附是否促进后部伸长。在目标I-B中，实验室将量化近轴中胚层中的纤连蛋白基质动态，并测试纤连蛋白原纤维生成是否有助于驱动近轴中胚层伸长。在目标II中，实验室研究了钙粘蛋白2和整合素5在调节近轴中胚层组装过程中纤连蛋白基质和细胞运动动力学转变中的作用。 在目标III中，该实验室测量了这些细胞和组织水平过程对产生后向定向细胞的贡献。 在延伸的tailbud的力量。