RUI: Investigating Hox gene regulation of paired appendage patterning in the basal actinopterygian, Polyodon

陆生(陆生)脊椎动物拥有其附肢的一个特殊区域，称为自足(手和脚；手指和脚趾)，这是它们的水生鱼类祖先所没有的。形成自肢动物的关键基因的变异产生了我们在自然界中看到的爬行、飞行和游泳适应的多样性，但也解释了人类手和脚中常见的先天性出生缺陷。此前，该实验室发现，与自体形成有关的基因，称为HOX基因，在原始的活鱼北美白对虾的鳍中活跃。这种鱼没有自动足部区域，也不是从有自动足部的祖先进化而来的。那么，为什么白鳍鱼有这些基因，它们的功能是什么呢？为了解决这些问题，这些研究人员正在使用这些基因的修改版本，这些基因的设计要么关闭基因功能，要么在发育中的白鳍鱼胚胎的鳍内将其放大到高于正常水平。这些结果应该揭示这些基因的正常功能，并解释与人类和小鼠出生缺陷数据相比，基因表达异常的结果。初步结果表明，以类似于人类和小鼠的方式，将特定的HOX基因与鳍的特定部分的形成联系在一起的骨骼结构的丢失模式。这些结果将提供对自动足部形成的重要见解，将回答进化问题，并有助于解决人类先天性自动足部出生缺陷的临床方法。此外，肯纳索州立大学的本科生将构成这项研究的核心，为众多学生提供研究经验，为他们在医学和生物科学领域的职业生涯做好准备。

Terrestrial (land living) vertebrates possess a specialized region of their appendages called the autopod (hands & feet; fingers & toes) which are not present in their aquatic fish ancestors. Variation in key genes that form the autopod generate the diversity of crawling, flying, and swimming adaptations we see in nature, but also explain common forms of congenital birth defects seen in human hands and feet. Previously, this laboratory discovered that genes involved in autopod formation, called Hox genes, are active in the fins of a primitive living fish, the North American paddlefish Polyodon spathula. This fish does not have an autopod region, nor did it evolve from an ancestor that had an autopod. Why then, do paddlefish have these genes and what is their function? To address these questions, these investigators are using modified versions of these genes designed to either shut down gene function or amplify it above normal levels within the developing fins of embryonic paddlefish. These results should reveal the normal function of these genes, and interpret the results of abnormal gene expression in comparison to data from human and mouse birth defects. Initial results demonstrate a pattern of loss of skeletal structures that links specific Hox genes to the formation of specific portions of the fin, in a manner similar to humans and mice. These results will provide significant insights into autopod formation that will answer both evolutionary questions and contribute to clinical approaches for addressing congenital autopod birth defects in humans. In addition, undergraduates at Kennesaw State will comprise the core of this research, providing numerous students with research experience to prepare them for careers in medicine and the biological sciences.