Doctoral Dissertation Research: Modeling developmental timing changes in human evolution

博士论文研究：模拟人类进化中的发育时间变化

基本信息

批准号：
1650824
负责人：
Joan Richtsmeier
金额：
$ 3.14万
依托单位：
Pennsylvania State Univ University Park
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-02-15 至 2018-01-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1650824&HistoricalAwards=false
关键词：
Doctoral Dissertation Research Modeling developmental

项目摘要

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.

人们认为，现代人类的许多解剖学和生理特征都通过早期生长和发育的时间变化而发展，而小鼠是研究这种变化的主要模型生物。该论文项目将开发出更准确的方法来确定胚胎发生过程中小鼠的发育年龄，并研究发育时机的变化，这可能驱动了解剖学特征的演变，这些特征将现代人类与最亲密的亲戚和祖先分开。这项研究产生的年龄估计方法将集成到一个免费的在线分期工具中。在该项目范围内进行的研究还将有助于为女性本科和高中生创造机会，以在数据收集和分析方面获得宝贵的经验，并在本地和国家座谈会上进行原始研究。这项研究的目的是解决有关发展时间的变化，即在速率，发作时间，或者在成年特定的特定型号的发展时期的发展时间的变化，无论是在速率上如何变化。实验系统提供了一种潜在的照明环境来解决这些问题，但是无法估计具有精确时间分辨率的胚胎的相对发育年龄仍然是一个重要的问题。该项目将建立一个分阶段系统，该系统将精确估计数小时内胚胎的相对发展，比现有的发展阶段系统更精确。该方法将仅使用鼠标后肢的照片估算胚胎第9天到第15天（E9-E15）之间的发育年龄，它代表了一种易于实现的工具，可减轻观察者间误差。然后，分期系统将用于确定人类特异性解剖结构的程度，例如面部的投影减少，是由发育时机的变化来产生的，通过研究携带突变的发育事件的速率和时间和时间，这些突变模拟了人类进化中发生的面部解剖结构的变化。这项研究的结果将为发展事件的基因型，表型和时机之间的关系提供宝贵而必要的澄清，从而为有关人类发展本质的问题提供创新的解决方案。