Quantification of the mechanics of vertebrate body elongation

描述(由申请人提供)：人造系统由具有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，生物系统会自我组装，在整个胚胎发生和器官发生过程中，使用基因控制来持续调节组织生物力学和组织功能。遗传分析揭示了发育过程中模式形成和细胞分化的许多基本原理。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不是很清楚。尾芽是发育中的脊椎动物胚胎的后部前沿，含有双潜能神经/中胚层干细胞以及脊髓和中胚层前体细胞。这项建议侧重于细胞-细胞和细胞-细胞外基质(ECM)黏附在定义延伸尾芽中的组织生物力学中的作用。假设这些组织之间依赖于纤维连接蛋白的机械耦合保持其后向定向力的平行方向。这种耦合增加了净后向定向力。在后旁轴中胚层内，假设纤维连接蛋白、纤维蛋白原和重塑驱动组织组装。组织组装需要通过钙粘连蛋白2整合细胞-细胞和细胞-细胞外基质黏附，钙粘连蛋白2调节纤维连接蛋白基质动力学，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-B中，该实验室将量化近轴中胚层中的纤维连接蛋白基质动力学，并测试纤维连接蛋白纤维形成是否有助于推动近轴中胚层的伸长。在AIM II中，实验室研究了钙粘附素2和整合素5在调节纤维连接蛋白基质中的转变以及在近轴向中胚层组装过程中细胞运动动力学方面的作用。在目标三中，实验室测量了这些细胞和组织水平的过程对后向定向的产生的贡献 伸展的尾芽中的力量。

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.