Cartilage is an important component of the vertebrate skeleton, but its evolutionary origin is poorly understood. Neural crest cells evolved in vertebrates and are required for the development of numerous vertebrate-specific characters, including cartilage within the head. The central goal of Dr. McCauley's research is to determine how the evolution and development of cartilage in vertebrates is related to the duplication of a single Sox E gene that is also present in invertebrates. The duplicated SoxE genes, Sox8, Sox9, and Sox10 play an important role in neural crest specification, but the importance of this gene duplication to the evolution of facial cartilage is not known. Dr. McCauley will use a molecular approach to interfere with the function of individual Sox proteins in a primitive vertebrate, the sea lamprey, to determine their roles in the development of cartilage from neural crest. The lamprey was chosen because of its primitive relationship to other vertebrate species. Results of this research are expected to reveal how lamprey SoxE genes regulate cartilage development and whether the fundamental developmental mechanisms of cartilage formation derived from neural crest cells are common to all vertebrates. This research will have broad impacts for the scientific and education communities. These studies will integrate research and higher education and will involve undergraduate students from diverse backgrounds in original laboratory research, in addition to training graduate students and post-doctoral investigators. Results will be of interest to a diverse audience since studies on the "primitive" lamprey are relevant to understanding the evolution and development of "advanced" model vertebrates. Techniques developed and used in this research will also be applied to a laboratory course currently under development by Dr. McCauley. Students in this course will learn how molecular, developmental, and bioinformatics tools are used to address questions related to the evolution of novel traits.
The intellectual merit of this project was to investigate the origin and history of cartilage developmental mechanisms in primitive vertebrates, and to determine how the evolution of chondrogenesis is related to gene duplication that occurred early in vertebrate evolution. One outcome of the project related to intellectual merit was to describe the process of cartilage development during embryogenesis in the sea lamprey. This outcome also resulted in the development of a new technique to observed cartilage in situ within embryos without sectioning the embryo. A second outcome was to show that a gene family (SoxE) required for cartilage development among jawed vertebrates is also required to regulate this process in the primitive sea lamprey. A third outcome was to show that the development of neural crest cells in the sea lamprey likely involves the same molecular mechanisms that are required for these cells to develop in all other vertebrates. The SoxE genes that underwent duplication early in vertebrate evolution appear to play roles in specification of the neural crest, and their differentiation into numerous derivatives both in lampreys (jawless vertebrates) and zebrafish (jawed vertebrates), suggesting that these mechanisms likely arose before jaweless and jawed vertebrates diverged during the early ancestry of the vertebrates. There are multiple outcomes regarding the broader impacts of this study. Dr. McCauley participated in a summer program at the Norman Public library to introduce elementary school aged children to science and research. The children were able to see and touch living lampreys, and to see the scientific and economic relevance of this animal. A second broader impact was to develop a laboratory based course that used tools developed for this project, and reagents used in it. The course has so far resulted in two students choosing to continue to pursue careers in science. During the funding period, 14 undergraduate students participated in the McCauley lab, contributing to this project. This number includes 10 women, and one native American. Three undergraduate students have been contributing authors on two publications. Dr. McCauley has also begun to involve a faculty member at East Central University with ongoing reserch in the McCauley Lab. Dr. Ken Andrews is a developmental biologist at East Central University in Ada, Oklahoma. His interest is to learn techniques that he can use in a laboratory course at East Central, to introduce undergraduate students to science and the potential for a science career. Undergraduates at East Central also have an opportuntiy to be involved with research in the McCauley Lab at OU. An intangible broader impact and benefit to society has been to increase knowledge. A tangible benefit to society has been to increase our understanding of how cartilage develops, and how the genes that regulate this process have retained this role following gene duplication early in vertebrate evolution. A second tangible benefit is the training that has been obtained by graduate students and undergraduates working on this project.
