Quantification of the mechanics of vertebrate body elongation

脊椎动物身体伸长力学的量化

基本信息

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
项目类别：
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

项目摘要

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）：人造系统由具有经过设计的物理特性的组件组装而成，以在最终组装中执行特定功能。相比之下，生物系统是自组装的，利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，但是，对于发育的生物力学和这些生物力学的遗传控制尚不清楚。生长中的脊椎动物胚胎，包含双能神经/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-细胞和细胞-细胞外基质（ECM）粘附在定义延伸尾芽的组织生物力学中的作用。重新认识到，这些组织之间的依赖于纤维连接的机械耦合保持其向后定向力的平行方向，这种耦合增加了后近轴内的净向后定向力。中胚层中，纤连蛋白纤维生成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流体的相变。在目标 I-A 中，实验室将检查轴旁中胚层和脊索之间的组织间粘附是否促进后部在 Aim I-B 中，实验室将量化近轴中胚层中的纤连蛋白基质动力学，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 Aim II 中，实验室将检查钙粘蛋白 2 和整合素的作用。 5 在轴旁中胚层组装过程中调节纤连蛋白基质和细胞运动动力学的转变在目标 III 中，实验室测量了这些细胞和组织水平过程对后向定向生成的贡献。尾芽伸出的力量。