Doctoral Dissertation Improvement: Dental Development in Pigs - A New Model for Studying the Evolutionary Morphology of Primate Teeth.

人类学家通常使用牙齿形态来研究现存和已灭绝灵长类动物的系统发育、咀嚼功能、行为和饮食。最近，人类学家开始假设参与牙齿发育的候选基因如何与灵长类动物的牙齿特征相关。这些候选基因被假设参与决定牙齿类型和影响尖形。然而，所有这些候选基因都是基于小鼠牙齿的发育研究。不幸的是，老鼠的牙齿与灵长类动物和大多数其他哺乳动物不同。这个项目将通过首次描述猪牙齿发育过程中的基因表达模式来解决这一缺陷。猪是一种具有更类似于灵长类动物的广义牙齿的哺乳动物。猪作为灵长类动物的研究模型是一个重大的改进，因为像灵长类动物一样，它们有门牙、犬齿、前磨牙和磨牙，以及牙齿替换。该项目还将建立在猪作为研究灵长类动物骨骼和牙齿生物学模型的广泛使用基础上。三个具体的目标将在详细介绍猪牙齿发育的遗传机制。首先，本研究将描述与猪牙齿类型建立相关的基因表达的分子模式。最重要的是，这将是第一个确定与犬和前磨牙发育相关的基因表达模式的研究。其次，提出的研究将确定基因表达模式如何与尖的位置和数量相关。第三，这项工作将确定在恒牙发育过程中是否观察到与乳牙发育过程中相似的基因表达模式。目前，所有将牙齿发育与牙齿形态联系起来的假设都是基于乳牙，而对灵长类动物牙齿形态的分析大多是基于恒牙。作为第一个在类似于灵长类动物的广义哺乳动物模型中详细描述牙齿发育过程中基因表达的研究，生物人类学将受益于能够将灵长类动物牙齿形态与发育遗传途径联系起来的更明智的假设。例如，对形成灵长类动物四种牙齿类型的基因的更好理解，可以帮助生物人类学家假设为什么某些灵长类动物群体，比如包括人类在内的群体，在进化过程中失去了牙齿。生物人类学家可以利用这项工作的结果来确定牙齿特征的相关性，用于系统发育研究，评估灵长类动物牙齿进化的可能遗传途径，并帮助破译灵长类动物牙齿形态进化的发育限制。此外，研究猪的结果可以应用于广泛的哺乳动物研究。最后，这项研究的新颖性将有助于弥合发育生物学和生物人类学之间的差距。这项工作的更广泛影响包括在生物人类学和发育生物学的几个领域培训一名女研究生。社会可以从这里收集的牙科发展的基础科学数据中受益，通过将其应用于牙科遗传学的临床研究。染色胚胎的图片将被放在一个数据库网站（http://www.neoucom.edu/dldd）上，并免费提供给公众用于研究和教育目的。

Anthropologists routinely use tooth form to study the phylogeny, masticatory function, behavior and diet of living and extinct primates. Recently, anthropologists have begun hypothesizing how candidate genes involved in tooth development relate to dental traits in primates. These candidate genes are hypothesized to be involved in determining tooth type and influencing cusp form. All of these candidate genes, however, are based on developmental studies of mouse teeth. Unfortunately, mice have highly derived dentitions that are dissimilar to primates and most other mammals. This project will begin to address this shortcoming by being the first to describe gene expression patterns during tooth development in pigs - a mammal with a generalized dentition more similar to primates. Pigs are a significant improvement as a model for studies of primates because, like primates, they have incisors, canines, premolars and molars as well as tooth replacement. This project will also build on the extensive use of pigs as models in studying primate bone and dental biology. Three specific aims will be addressed in detailing the genetic mechanisms of tooth development in pigs. First, this research will describe molecular patterns of gene expression involved in establishing tooth type in pigs. Most importantly, this will be the first study identifying gene expression patterns related to the development of canines and premolars. Second, the proposed research will determine how gene expression patterns relate to cusp placement and number. Third, this work will determine if similar gene expression patterns are observed during permanent tooth development as seen during deciduous tooth development. All hypotheses linking dental development to tooth form are currently based on the deciduous teeth, while most analyses on primate dental morphology are on permanent teeth.As the first study detailing gene expression during tooth development in a generalized mammalian model similar to primates, biological anthropology will benefit from being able to formulate more informed hypotheses linking primate dental form to developmental genetic pathways. For example, an improved understanding of the genes that contribute to forming each of the four tooth types found in primates can be useful for biological anthropologists hypothesizing why certain primate groups, such as the group including humans, have lost teeth during their evolution. Biological anthropologist can use the results of this work to identify dental character correlations for phylogenetic studies, to evaluate possible genetic pathways underlying primate dental evolution, and to help decipher developmental constraints on the evolution of primate tooth form. Furthermore, results from studying pigs can be applied to research on a wide range of mammals. Finally, the novelty of this research will help bridge a gap between developmental biology and biological anthropology.Broader impacts from this work include training of a female graduate student in several areas of biological anthropology and developmental biology. Society may benefit from the basic science data on dental development collected here through its application to clinical studies of dental genetics. Pictures of stained embryos will be placed on a database website (http://www.neoucom.edu/dldd) and made freely available to the public for research and educational purposes.