RUI: Elucidating The Role of Hoxa-5 In Cervical Somite Morphogenesis and Evolution

RUI：阐明 Hoxa-5 在颈部体节形态发生和进化中的作用

• 批准号: 0818223
• 负责人: Jennifer Mansfield
• 金额: $ 40.49万
• 依托单位: Barnard College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0818223&HistoricalAwards=false
• 关键词: RUI; Elucidating; Role; Hoxa; Cervical

One of the earliest events in animal development is the establishment of the main, head-to-tail body axis. Embryonic cells and tissues must receive a molecular "address" along this axis, and then develop appropriately for their location. In most animals, these processes are regulated at several steps by the highly conserved Hox gene family. Hox proteins regulate the expression of other, mostly unknown, genes, and play central roles in both the development and evolution of animal body plans. Despite enormous progress toward understanding the roles of Hox proteins in development and evolution, we still know relatively little about which cellular processes they regulate in the various tissues in which they act, especially in vertebrates. This project will examine the cellular processes regulated by one Hox gene, Hoxa5, during the development of vertebrate axial tissues (bone, muscle, and connective tissues of the vertebral column and ribs). Molecular genetic methods will be employed to ask (1) which cells within developing mouse express, or have a history of expressing, Hoxa5, (2) whether there a lineage relationship between cells that express Hoxa5 at different stages of embryogenesis, (3) how cells with a history of having expressed Hoxa5 differ from cells that do not, both in terms of their development and eventual fates, and finally, (3) how changes in Hoxa5 expression influence the differentiation of vertebral segments in chick embryos. Together, these approaches are aimed at teasing apart the elusive and context-dependent roles for this Hox protein in one embryonic tissue in which it acts. In addition, the genetic reagents produced by this work will be useful for future studies examining Hoxa5's roles in other tissues. This research will be conducted at Barnard College: an undergraduate, liberal arts college for women. Undergraduates will collaborate with the PI and a research technician in all aspects of this work, from experimental design to conducting experiments to analysis of results. The broader impacts of this study are (1) to provide new insight into how Hox proteins regulate patterning and differentiation of vertebrate tissues and (2) to provide a hands-on training experience for undergraduate researchers in a lab environment where they are the driving force behind the research.

动物发育中最早的事件之一是头尾相连的主体轴的建立。胚胎细胞和组织必须沿着这个轴获得一个分子“地址”，然后根据它们的位置适当地发育。在大多数动物中，这些过程在几个步骤中受到高度保守的HOX基因家族的调控。HOX蛋白调节其他大多数未知基因的表达，并在动物身体计划的发展和进化中发挥核心作用。尽管在理解HOX蛋白在发育和进化中的作用方面取得了巨大的进展，但我们仍然对它们在不同组织中调节哪些细胞过程知之甚少，特别是在脊椎动物中。这个项目将研究一个HOX基因Hoxa5在脊椎动物轴组织(骨、肌肉以及脊柱和肋骨的结缔组织)发育过程中所调控的细胞过程。分子遗传学方法将被用来询问(1)发育中的小鼠中哪些细胞表达或有表达Hoxa5的历史，(2)在胚胎发育的不同阶段表达Hoxa5的细胞之间是否存在谱系关系，(3)有表达Hoxa5的细胞与没有表达Hoxa5的细胞在发育和最终命运方面的不同，以及(3)Hoxa5表达的变化如何影响鸡胚胎脊椎节段的分化。总之，这些方法的目的是梳理出这种Hox蛋白在它所作用的一个胚胎组织中难以捉摸的和上下文相关的角色。此外，这项工作产生的遗传试剂将有助于未来研究Hoxa5‘S在其他组织中的作用。这项研究将在巴纳德学院进行，巴纳德学院是一所面向女性的本科文理学院。本科生将在这项工作的所有方面与PI和一名研究技术人员合作，从实验设计到进行实验再到结果分析。这项研究的更广泛的影响是(1)为HOX蛋白如何调控脊椎动物组织的模式和分化提供新的见解，以及(2)为本科生研究人员在实验室环境中提供实践培训体验，在实验室环境中，他们是研究的驱动力。