The Mechanics of Lung Development in Three Different Species

三种不同物种的肺发育机制

• 批准号: 1435853
• 负责人: Celeste Nelson
• 金额: $ 40万
• 依托单位: Princeton University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1435853&HistoricalAwards=false
• 关键词: Mechanics; Lung; Development; Three; Different

Morphogenesis is the process by which simple tissues fold into the complex shapes of mature organs, such as the branching airways of the lung. This tissue folding is caused by patterns of mechanical forces (pushing and pulling the tissue) that are induced by the expression of different genes throughout the tissue. The final shapes of the lungs of mammals, birds, and reptiles are vastly different, suggesting that the mechanical forces and genes expressed are different as well. This award supports fundamental research to define the gene expression changes and mechanical forces that fold the airways of the lungs in three different species (mouse, chicken, and alligator). Understanding what is unique and what is conserved between lungs of different species will provide insight into how different organs evolved over time. Additionally, being able to manipulate the expression of genes to control organ development is critical for tissue engineering applications for the biomedical and healthcare industries. Results from this research will therefore have economic and societal benefits for the United States. This research combines techniques and insights from several disciplines, including developmental biology, mechanobiology, and biomedical engineering. This interdisciplinary approach will help broaden the participation of underrepresented minority groups (at the undergraduate and high school levels) and enhance outreach interactions with the lay population.Mammals, birds, and reptiles have evolved different anatomical strategies for the conduction and diffusion of air through the lungs, which must result from differences in airway morphogenesis in the embryo. The objective of this project is to define and quantify these evolutionary morphogenetic differences. The research team will use three-dimensional traction force microscopy, real time confocal imaging, and continuum mechanical modeling to quantify the forces exerted during morphogenesis of the distinct airway architectures of embryonic mice, chicks, and alligators. In parallel, high-throughput gene expression analysis will be conducted for each morphogenetic movement in each species. These analyses will reveal the distinct gene expression changes that control mechanical forces within the epithelium as it folds lateral branches (mammals and birds), bifurcating branches (mammals and reptiles), and anastomosing airways (birds and reptiles). This research adopts for the first time the principles of mechanobiology within the framework of evolutionary developmental biology to create a comprehensive physical description of tissue morphogenesis, and will uncover the basic mechanical differences underlying lung development in different species.

形态发生是简单组织折叠成成熟器官复杂形状的过程，例如肺的分支气道。这种组织折叠是由机械力模式（推拉组织）引起的，机械力模式是由整个组织中不同基因的表达引起的。哺乳动物、鸟类和爬行动物的肺部最终形状有很大不同，这表明机械力和表达的基因也不同。该奖项支持基础研究，以定义三种不同物种（小鼠、鸡和鳄鱼）肺部气道折叠的基因表达变化和机械力。了解不同物种的肺之间的独特性和保守性将有助于了解不同器官如何随着时间的推移而进化。此外，能够操纵基因表达来控制器官发育对于生物医学和医疗保健行业的组织工程应用至关重要。因此，这项研究的结果将为美国带来经济和社会效益。这项研究结合了多个学科的技术和见解，包括发育生物学、机械生物学和生物医学工程。这种跨学科方法将有助于扩大代表性不足的少数群体（在本科和高中水平）的参与，并增强与非专业人群的互动。哺乳动物、鸟类和爬行动物已经进化出不同的解剖策略来通过肺部传导和扩散空气，这必定是由于胚胎中气道形态发生的差异造成的。该项目的目标是定义和量化这些进化形态发生差异。研究小组将使用三维牵引力显微镜、实时共焦成像和连续力学模型来量化胚胎小鼠、雏鸡和鳄鱼的独特气道结构形态发生过程中所施加的力。同时，将对每个物种的每个形态发生运动进行高通量基因表达分析。这些分析将揭示在上皮折叠侧枝（哺乳动物和鸟类）、分叉枝（哺乳动物和爬行动物）和吻合气道（鸟类和爬行动物）时控制上皮内机械力的独特基因表达变化。这项研究首次采用进化发育生物学框架内的力学生物学原理，对组织形态发生进行全面的物理描述，并将揭示不同物种肺发育的基本力学差异。