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

包括人类在内的灵长类物种有不同的牙齿模式，反映了不同的饮食和生态特化，但这些差异背后的遗传机制尚不清楚。这项研究的目标是确定在人类和其他灵长类动物中负责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、尖牙、前磨牙)的基因表达差异。这项新颖的潜在变革性研究的发现不仅将通过为牙齿进化研究提供信息来推动科学发展，而且可能通过有助于理解和未来治疗人类牙齿畸形而产生社会影响。在这项为期24个月的研究中，将使用尖端的RNA测序技术来量化人类牙齿发育的关键阶段(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。识别牙齿尖端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模式的，以及哪些牙齿基因在哺乳动物进化过程中得到了保护。这项研究将产生新的、可测试的假说，即基因表达的差异如何导致牙齿的变异和在灭绝和灭绝的灵长类物种中看到的适应。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目前的牙齿多样性，因为直到不同形状牙齿的形成得到充分表征，才能发现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为牙齿解剖异常的遗传基础提供潜在的变革性新信息。该项目还将提供学生培训和科学推广，包括一个指导探究实验室，在那里本科生将测试哺乳动物牙齿形态、功能和饮食之间的对应假设，并了解不同形状的牙齿是如何发育的。

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.