DISSERTATION RESEARCH: Mechanisms of Mammalian Middle Ear Ossicle Transition from the Reptilian Jaw Joint

从爬行动物到哺乳动物的转变是导致人类最终进化的最重要的事件之一。这种转变的特点是有许多变化，其中最重要的是哺乳动物中耳的进化。该项目的目标是以负鼠物种为模式生物，研究哺乳动物中耳进化的发育基础。由于负鼠是原始哺乳动物，它们可以为哺乳动物的进化提供重要的见解，而这个项目将产生的对耳朵发育的更好的理解有可能对人类健康产生积极的影响。该项目还将作为对几名本科生的STEM培训和面向K-12学生的社区外展活动的基础。这个项目的结果也被纳入了PBS的三集纪录片，纪录片改编自尼尔·舒宾的畅销书《你的内心之鱼》。爬行动物的下巴由多块骨头组成，而爬行动物的中耳只有一块骨头。相反，哺乳动物的下巴只有一块骨头，而哺乳动物的中耳则有多块骨头。通过古生物学和胚胎学的研究表明，哺乳动物中耳中的多余骨骼来自爬行动物下巴中的多余骨骼。与颌骨分离将使中耳成分的进化具有更大的灵活性，从而提高听力敏感度和扩大频率范围。在化石记录中从爬行动物到哺乳动物的转变中观察到的中耳变化也发生在负鼠的发育过程中。负鼠出生时的中耳与爬行动物相似，但成年后的中耳是哺乳动物，这为研究哺乳动物中耳骨在当前活着的有机体中的进化发展提供了独特的机会，而不是通过化石。该项目基于对过渡的详细描述，使用微型计算机断层扫描，从出生开始每隔五天创建一次三维图像，并通过在所述阶段进行冷冻切割来研究过渡背后的细胞过程，然后进行细胞增殖和凋亡的免疫组织化学研究。该项目将使用原位杂交和RNA测序来揭示导致这种转变的基因。特定基因(如TGTbr2和Eya1)表达和浓度的时间变化预计与Meckel软骨的分离和听小骨功能的变化有关。这项研究将确定负鼠中的活性基因是否也在胎盘哺乳动物的中耳区表达。该项目将比较负鼠发育过程中发生的转变与化石记录中观察到的导致早期哺乳动物血统的转变。

The transition from reptile to mammal was one of the most important events in leading to the eventual evolution of humans. This transition is characterized by many changes, one of the most important is the evolution of the mammalian middle ear. The goal of this project is to investigate the developmental basis of the evolution of the mammalian middle ear, using an opossum species as a model organism. Because opossum are primitive mammals, they can provide significant insights into mammalian evolution, and the improved understanding of ear development that this project will generate has the potential to positively impact human health. This project will also serve as a foundation for the STEM training of several undergraduates and for community outreach events geared toward K-12 students. Results of this project are also being incorporated into a three-part PBS documentary based upon Neil Shubin's best-selling book, Your Inner Fish. The reptilian jaw consists of multiple bones, while there is only a single bone in the reptile middle ear. Conversely, the mammalian jaw consists of a single bone, while there are multiple bones in the mammal middle ear. It has been shown, via paleontology and embryology, that the extra bones in the mammalian middle ear originated from the extra bones in the reptilian jaw. Separation from the jaw would allow more flexibility in the evolution of the middle ear elements, resulting in increased hearing sensitivity and amplified frequency range. The middle ear changes observed in the transition from reptiles to mammals in the fossil record also occur during development in opossum. Opossum are born with a middle ear similar to reptiles, but in adults the middle ear is mammalian, providing a unique opportunity to study the evolutionary development of mammalian middle ear bones in an currently living organism rather than with fossils. The project is based on a detailed characterization of the transition using micro-computed tomography scans to create three-dimensional images at five day intervals, beginning at birth, and studying the cellular processes underlying the transition by cryosectioning at the noted stages, followed by immunohistochemistry for cell proliferation and apoptosis. The project will uncover the genes responsible for the transition using in situ hybridization and RNA sequencing. Alterations in the timing of expression and concentration of particular genes (e.g., TGTbr2 and Eya1) are expected to be correlated with the separation of Meckel's cartilage and functional changes in the ossicles. The research will determine if the active genes in opossum are also expressed in the middle ear region of placental mammals. The project will compare the transition that occurs during opossum development to that observed in fossil record leading to early mammal lineages.