Doctoral Dissertation Research: Documenting differences in gene expression during human tooth development to understand the evolution of the primate dentition

博士论文研究：记录人类牙齿发育过程中基因表达的差异，以了解灵长类动物牙列的进化

• 批准号: 1455572
• 负责人: Martin Cohn
• 金额: $ 3万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1455572&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Research; Documenting; differences

Primate species, including humans, have diverse dental patterns that reflect different dietary and ecological specializations, but the genetic mechanisms that underlie these differences are poorly understood. The goal of this study is to identify specific genes that are responsible for tooth formation and tooth shape in humans and other primates. The investigators will use human and mouse dental tissues in conjunction with state-of-the-art molecular techniques to identify genes and measure differences in gene expression across tooth types (i.e. incisors, canines, premolars). The findings from this novel and potentially transformative study will not only advance science by informing research on dental evolution, but may have societal impact by contributing to the understanding and future treatment of dental malformations in humans. In this 24 month study, cutting-edge RNA sequencing technology will be used to quantify levels of expression of all genes at a key stage in human tooth development (cap stage), and to compare dental gene expression in humans and mice. Identifying individual genes that are the primary determinants of a tooth's cusp pattern will help explain how the human dentition is patterned during development and what dental genes have been conserved during mammalian evolution. This research will result in novel, testable hypotheses of how differences in gene expression may produce dental variation and adaptations seen in extinct and extant primate species. This represents a first step towards understanding evolutionary transitions that gave rise to the present dental diversity among primates because the genetic and developmental drivers of changes in tooth shape cannot be uncovered until the formation of differently shaped teeth is fully characterized. In addition, knowledge of the genetic components required for tooth formation will provide potentially transformative new information on the genetic underpinnings of anatomical anomalies in teeth. The project will also provide student training and scientific outreach, including a guided-inquiry lab in which undergraduate students will test hypotheses of the correspondence between tooth morphology, function, and diet in mammals and learn how differently-shaped teeth develop.

灵长类物种，包括人类，有不同的牙齿模式，反映了不同的饮食和生态专业化，但这些差异背后的遗传机制知之甚少。这项研究的目的是确定负责人类和其他灵长类动物牙齿形成和牙齿形状的特定基因。研究人员将使用人类和小鼠的牙齿组织结合最先进的分子技术来识别基因，并测量不同牙齿类型（即门牙，犬齿，前磨牙）的基因表达差异。这项新的和潜在的变革性研究的结果不仅将通过为牙齿进化研究提供信息来推进科学，而且可能通过促进对人类牙齿畸形的理解和未来治疗来产生社会影响。在这项为期24个月的研究中，尖端的RNA测序技术将用于量化人类牙齿发育关键阶段（帽状期）所有基因的表达水平，并比较人类和小鼠的牙齿基因表达。确定牙齿牙尖模式的主要决定因素的单个基因将有助于解释人类牙列在发育过程中是如何形成的，以及在哺乳动物进化过程中哪些牙齿基因是保守的。这项研究将导致新的，可测试的假设，基因表达的差异如何可能产生牙齿的变化和适应看到灭绝和现存的灵长类动物物种。这代表了理解进化转变的第一步，这些进化转变导致了灵长类动物之间的牙齿多样性，因为在不同形状牙齿的形成得到充分表征之前，无法揭示牙齿形状变化的遗传和发育驱动因素。此外，牙齿形成所需的遗传成分的知识将提供潜在的变革性的牙齿解剖异常的遗传基础的新信息。该项目还将提供学生培训和科学推广，包括引导调查实验室，本科生将在其中测试牙齿形态，功能和哺乳动物饮食之间的对应关系的假设，并了解不同形状的牙齿是如何发育的。