Evolution and Development of Vertebrate Hox14 Genes

脊椎动物Hox14基因的进化和发育

• 批准号: 0719558
• 负责人: Chris Amemiya
• 金额: $ 39.8万
• 依托单位: Benaroya Research Institute at Virginia Mason
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0719558&HistoricalAwards=false
• 关键词: Evolution; Development; Vertebrate; Hox14; Genes

This research will investigate a paralogous group of hitherto unknown vertebrate Hox genes, Hox14. Genes encoding Hoxa14 and Hoxd14 were recently discovered in the coelacanth and elasmobranchs, respectively, and preliminary data suggest that these genes are biologically functional. The findings raise numerous questions germane to the evolution and development of these genes. Four Specific Aims will be pursued. The first two are to clone and genomically-characterize Hox14 genes from the lamprey and lungfish, respectively. Strategies have been designed to take advantage of the laboratory's expertise in the genomic isolation and characterization of vertebrate Hox genes. The third Aim will examine and compare expression patterns of Hox14 genes in both the skate and the lamprey. Functional experiments will be undertaken in the lamprey in order to assess the direct role of Hox14 in embryological development. The fourth Aim will delineate and examine the developmental role of putative cis regulatory elements in the vicinity of the Hoxa14 and Hoxd14 coding sequences. One such element has been shown to be involved in a clear and consistent phenotype in vivo in three surrogate systems, thus strengthening the rationale for this Aim. The four Specific Aims are independent and not contingent on one another. The overarching goal of this research is to understand the role that Hox14 genes may have played in vertebrate evolution and development. The discovery of Hox14 genes in vertebrates was unexpected and their maintenance in distinct vertebrate lineages that diverged some 400 million years ago suggests that they may have played a key developmental role. The "broad impact" of this research is measured in two ways: (1) through employment of highly interdisciplinary approaches to problem solving, including genomics, evolutionary biology, developmental biology and natural history; and (2) by providing a wealth of research and educational resources and opportunities. The research resources include publicly available gene libraries and other reagents. The training opportunities include traineeships for undergraduates of underrepresented minorities.

这项研究将调查迄今为止未知的脊椎动物Hox基因的旁系同源群Hox 14。 最近在腔棘鱼和板鳃类中分别发现了编码Hoxa 14和Hoxd 14的基因，初步数据表明这些基因具有生物学功能。这些发现提出了许多与这些基因的进化和发展密切相关的问题。将实现四个具体目标。前两个是从七鳃鳗和肺鱼中分别克隆和基因组学表征Hox 14基因。策略已被设计为利用实验室的专长，在基因组分离和脊椎动物Hox基因的特性。第三个目标将检查和比较Hox 14基因在溜冰鞋和七鳃鳗的表达模式。将在七鳃鳗中进行功能实验，以评估Hox 14在胚胎发育中的直接作用。第四个目标将描绘和研究的发展作用，推定的顺式调控元件附近的Hoxa 14和Hoxd 14编码序列。一个这样的元素已被证明是在一个明确的和一致的表型在体内三个替代系统，从而加强了这个目标的理由。这四个具体目标是独立的，彼此之间并不相互依赖。 这项研究的首要目标是了解Hox 14基因在脊椎动物进化和发育中可能发挥的作用。Hox 14基因在脊椎动物中的发现是出乎意料的，它们在大约4亿年前分化的不同脊椎动物谱系中的维持表明它们可能发挥了关键的发育作用。 这一研究的“广泛影响”可以从两个方面来衡量：（1）通过采用高度跨学科的方法来解决问题，包括基因组学、进化生物学、发育生物学和自然历史;（2）提供丰富的研究和教育资源和机会。研究资源包括公开的基因文库和其他试剂。培训机会包括为代表性不足的少数民族的大学生提供培训。