Evolution and Development of the Hominoid Wrist

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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.