Morphogenetic Tissue Movements in Early Embryos

早期胚胎中的形态发生组织运动

• 批准号: 8921214
• 负责人: ANDRAS CZIROK
• 金额: $ 28.64万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8921214
• 关键词: Animal Model; Applications Grants; Behavior; Biological Assay; Biomechanics; Birds; Blood; Cartilage; Cells; Complex; Computer Simulation; Congenital Abnormality; Contracts; Cues; Data; Development; Discipline; Embryo; Endoderm Cell; Environment; Event; Exhibits; Extracellular Matrix; Future; Gel; Germ Layers; Goals; Growth; Health; Human; Image; Image Analysis; Individual; Knowledge; Laws; Life; Link; Measurement; Mechanical Stress; Mechanics; Methods; Microscopy; Modeling; Molds; Morphogenesis; Morphology; Movement; Normal tissue morphology; Optics; Organ; Outcome; Pathologic Processes; Physiological Processes; Positioning Attribute; Primitive foregut structure; Process; Property; Relaxation; Research; Rheology; Stress; Structure; Tissue Engineering; Tissues; Traction; Wound Healing; base; blastomere structure; bone; cancer cell; cell motility; computerized tools; insight; mathematical model; millimeter; molecular imaging

DESCRIPTION (provided by applicant): Tissue engineering, the controlled construction of tissues - cells and their extracellular matrix (ECM) environment - is a promising avenue of future biomedical applications. To realize this possibility, the dynamic and mutually interdependent relationship between cells and ECM has to be understood. The long-term goal of our research is to understand the interplay between cell and tissue dynamics during embryonic morphogenesis. In particular, the early avian embryo is an anatomically and experimentally tractable warm-blooded model organism, exhibiting a morphogenic sequence comparable in complexity to that of human embryos. The objective of this grant application is to provide a comprehensive and predictive computational model of the caudal avian embryo during the first day of development. The model will explain how tissue movements arise from the collective action of its constituent cells. Our central hypothesis is that the body plan of early amniote embryos is not established by "conventional" cell motility -- i.e., cells migrating on a rigid substrate to pre-defined positins following environmental cues. Instead, germ layers and the entire embryo morphology are molded to a large extent by cell- exerted mechanical forces (stresses) and their controlled dissipation/relaxation as well as cells moving by gaining traction from adjacent cells, cellular activities dubbed as "nonconventional motility" in this application. We propose a synergistic approach combining advanced imaging, molecular and mechanical perturbations, micro-rheology measurements, and computational modeling. Specifically, we propose to i) determine the contributions of "conventional" vs. "non-conventional" cell motility in the morphogenetic processes of early avian embryos, ii) identify the mechanical basis of "non- conventional" cell motility in early avian embryos, and iii) develop computational models to derive tissue-level growth laws from cellular activities. The empirical data generated during the proposed research will fill a gap in our knowledge of how most embryonic cells and the surrounding ECM moves during early development, and what are the corresponding spatio-temporal dynamics of mechanical stress within the tissues. The data will clarify the mechanism of a prevalent yet understudied mode of collective cell motility. Our efforts will create the first model that explain complex movements of a millimeter-sized piece of living material by resolving and relating events both at the tissue and individual cell level. Advanced optical microscopy and image analysis methods, as well as the resulting computational tools will enable future studies of more differentiated and functional tissues and increase our understanding of the tissue mechanics underlying physiological and pathological processes: such as bone and cartilage remodeling, wound healing or malignant cell invasion.

描述（由申请人提供）：组织工程，组织的受控构造 - 细胞及其细胞外基质（ECM）环境 - 是未来生物医学应用的有前途的途径。要实现这种可能性，必须了解细胞与ECM之间的动态和相互依存关系。我们研究的长期目标是了解胚胎形态发生过程中细胞和组织动力学之间的相互作用。特别是，早期的鸟类胚胎是一种解剖学和实验性的暖血文模型生物，表现出与人类胚胎相比的形态学序列。该赠款应用的目的是在开发的第一天提供尾鸟类胚胎的全面和预测性计算模型。该模型将解释组织运动是如何由其组成细胞的集体作用引起的。我们的中心假设是，早期羊膜胚胎的身体计划不是由“常规”细胞运动能力建立的，即，在环境提示后，在刚性底物上迁移到预定的阳性蛋白上的细胞。取而代之的是，细胞层和整个胚胎形态在很大程度上被细胞的机械力（应力）及其受控的耗散/弛豫以及通过从相邻细胞中获得吸引而移动的细胞，在此应用中被称为“非惯性运动”。我们提出了一种协同方法，结合了高级成像，分子和机械扰动，微得分测量和计算建模。具体而言，我们向i）提出建议）确定“常规”与“非惯性”细胞运动在早期鸟类胚胎的形态发生过程中的贡献，ii）确定在早期禽胚中“非常规”细胞运动的机械基础，以及iii）开发计算模型，从而从细胞中得出组织层面的生长法。在拟议的研究期间产生的经验数据将填补我们对大多数胚胎细胞和周围ECM在早期发育过程中如何移动的知识，以及组织内机械应力的相应时空动力学是什么。数据将阐明普遍却研究的集体细胞运动模式的机制。我们的努力将创建第一个模型，该模型通过在组织和单个细胞水平上解决和关联事件来解释毫米大小的生物材料的复杂运动。先进的光学显微镜和图像分析方法以及所得的计算工具将使未来的分化和功能性组织的研究并增强我们对生理和病理过程中的组织力学的理解：骨骼和软骨重塑，伤口愈合或恶性细胞入侵。