Doctoral Dissertation Research: Modeling developmental timing changes in human evolution

现代人的许多解剖和生理特征被认为是通过早期生长和发育时间的变化而进化的，而小鼠是研究这种变化的主要模式生物。本论文项目将开发更准确的方法来确定胚胎发生期间小鼠的发育年龄，并研究发育时间的变化，这些变化可能推动了将现代人与其近亲和祖先分开的解剖特征的进化。这项研究产生的年龄估计方法将被整合到一个免费提供的在线分期工具中。在本项目范围内进行的研究也将有助于为女大学生和高中学生创造机会，获得数据收集和分析的宝贵经验，并在地方和国家专题讨论会上展示原创性研究。本研究的目的是解决长期存在的问题，即发育时间的变化，无论是在胚胎发生过程中特定解剖特征的发育速度、开始时间还是偏移时间，如何影响成体形态。实验系统为解决这些问题提供了潜在的启发性背景，但是无法用精确的时间分辨率估计胚胎的相对发育年龄仍然是一个重大问题。该项目将建立一个分期系统，以小时为单位精确估计胚胎的相对发育，比现有的发育分期系统精确一个数量级。该方法仅使用小鼠后肢的照片就可以估计胚胎第9天至胚胎第15天（E9-E15）之间的发育年龄，是一种易于实现的工具，可以减少观察者之间的误差。然后，通过研究携带模拟人类进化中面部解剖变化的突变的小鼠的发育事件的速率和时间，分期系统将被用于确定人类特定解剖结构（如面部投影减少）在多大程度上是由发育时间的变化产生的。这项研究的结果将为基因型、表型和发育事件时间之间的关系提供有价值和必要的澄清，为有关人类发展本质的问题提供创新的解决方案。

Many anatomical and physiological characteristics of modern humans are thought to have evolved through changes in the timing of early growth and development, and the mouse is a primary model organism for studying such changes. This dissertation project will develop more accurate methods for determining the developmental age of mice during embryogenesis and investigate changes in developmental timing that may have driven the evolution of anatomical features that separate modern humans from their closest relatives and ancestors. The age estimation methodology produced by this research will be integrated into a freely available, online staging tool. Research conducted within the scope of this project will also help to create opportunities for female undergraduate and high school students to gain valuable experience in data collection and analysis, and to present original research at local and national symposia.The purpose of this research is to address long-standing questions about how changes in the timing of development, either in the rate, the onset time, or the offset time of the development of specific anatomical features during embryogenesis, affect adult morphology. Experimental systems provide a potentially illuminating context to address these questions, but the inability to estimate the relative developmental age of an embryo with precise temporal resolution remains a significant problem. This project will establish a staging system that will precisely estimate the relative development of an embryo in hours, an order of magnitude more precise than existing developmental staging systems. The method, which will estimate developmental ages between embryonic day 9 and embryonic day 15 (E9-E15) using only a photograph of the mouse hindlimb, represents an easy-to-implement tool that mitigates interobserver error. The staging system will then be used to determine the extent to which human-specific anatomy, such as the reduced projection of the face, is produced by a shift in developmental timing, by studying the rate and timing of developmental events in mice carrying mutations that simulate changes in facial anatomy that occurred in human evolution. The results of this research will provide valuable and necessary clarification of the relationships among genotype, phenotype, and timing of developmental events, producing innovative solutions to questions about the nature of human development.