Evolution and Development of the Hominoid Wrist

人类和猿手腕的解剖结构反映了与攀爬、使用前肢支撑和制造工具有关的重要行为适应。手腕的形状在很大程度上是由在发育和生长过程中控制其表达的基因决定的。本研究的目的是发现在小鼠手腕发育过程中活跃的基因和增强子，并将它们与类似的灵长类基因组序列进行比较，以重建人类手腕的进化。这个项目为不同的学生群体提供了在发育生物学和比较基因组学中应用前沿方法的实验室研究机会。PI将通过费城医师学院（CPP）的教育和公共倡议中心（CEPI）向费城地区服务不足的高中生进行科学推广。该项目的发展进化方法和发现也将被纳入STEM领域的本科和研究生课程。相对于灵长类祖先，手腕在人类进化过程中经历了两次重大转变。首先，现存猿类和人类的一个决定性特征是尺骨和腕骨之间失去了接触。不幸的是，化石记录不足以确定我们更像猴子的祖先发生这种关键变化的时间。因此，在早期猿类中，尺骨和手腕之间的接触丧失是一次发生还是多次平行发生，目前尚不清楚。其次，人类的梨状骨，相当于脚踝的后跟，由于失去了生长板而缩短了，这一转变可能反映了我们采用石器制造和使用。在实验室中使用RNA-seq和ATAC-seq等新技术，可以揭示在发育中的小鼠手腕内侧和外侧部分活跃的基因和增强子。这一知识，当与灵长类动物的基因组比较相结合时，允许测试关于这些转变时间的假设。此外，该方法还可以揭示类人猿和人类腕部重组和鱼状生长板缺失的基因和调控序列。这些信息将提高我们对人类起源和哺乳动物骨骼发育本质的理解。

The anatomy of human and ape wrists reflect important behavioral adaptations related to climbing, using the forelimb for support, and tool making. The shape of the wrist is determined in large part by the genes that control their expression during development and growth. The goal of this research is to discover the genes and enhancers active during mouse wrist development and compare them to similar primate genomic sequences to reconstruct the evolution of the human wrist. This project expands laboratory research opportunities for a diverse body of students in the application of cutting-edge methods in developmental biology and comparative genomics. The PI will conduct science outreach to underserved high school students in the Philadelphia area through the Center for Education and Public Initiatives (CEPI) at the College of Physicians of Philadelphia (CPP). The developmental evolutionary approaches and findings from this project will also be incorporated into undergraduate and graduate curricula in STEM fields.The wrist has undergone two major transitions over the course of human evolution relative to ancestral primates. First, a defining character of living apes and humans is the loss the contact between the ulna and the wrist skeleton. Unfortunately, the fossil record is not sufficient to determine when this crucial change occurred from our more monkey-like ancestors. Therefore, it is unresolved whether the loss of contact between the ulna and wrist has occurred once in early apes or multiple times in parallel. Second, the pisiform, which is equivalent to the heel in the ankle, has shortened in humans through the loss of a growth plate, a shift that may reflect our adoption of stone tool manufacture and use. The use of new technologies in the lab, such as RNA-seq and ATAC-seq, can reveal the genes and enhancers that are active in medial and lateral portions of the developing mouse wrist. This knowledge, when combined with genomic comparisons among primates, permits the testing of hypotheses concerning the timing of these transitions. Furthermore, this approach can reveal the genes and regulatory sequences involved in the reorganization of the ape and human wrist and the loss of the pisiform growth plate. Such information will improve our understanding of human origins and the nature of mammalian skeletal development in general.