CAREER - Building the Vertebrate Body with Axial Stem Cells

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The human body plan, along with the body plan of all other vertebrates, is established during embryogenesis in a progressive manner, with the head forming first and the rest of the body growing sequentially away from the head. Recent work in vertebrate animal models revealed the unexpected finding that a population of stem cells, called axial stem cells, fuels the process of body growth over long periods of time by contributing new cells to the differentiating spinal cord, skeletal muscle, and blood vessels, among others. Since axial stem cells have only recently been discovered, there is a severe paucity of information regarding their normal development in any species. The goal of this project is to establish the molecular mechanisms of axial stem cell induction, maintenance, and fate specification in the zebrafish. This work will provide critical insight into how the vertebrate body is created, as well as shed light on the mechanisms leading to body plan diversity across the animal kingdom. Undergraduate students will participate in this project, providing them with a cutting edge research experience. Additionally, the project will also use zebrafish as a tool to teach biological principles to high school students, and to get them excited about developmental biology. This will be accomplished through two mechanisms: 1) the creation of a professional development course for high school teachers that will provide them with the training necessary to run zebrafish development teaching laboratories at their schools, and 2) a hands-on laboratory module for high school students. These programs are designed to meet the needs of the changing emphasis on laboratory-based hands on learning, with a particular emphasis on providing these educational opportunities to high-needs school districts.Zebrafish offer an unparalleled system to investigate axial stem cell biology. The transparent embryos, along with genetic and cell transplantation tools, allow for the precise determination of the cell-autonomous, temporal role of pathways and genes functioning within axial stem cells in vivo. Using these methods, this project investigates three key aspects of axial stem cells, including 1) how axial stem cells are induced during the gastrula stage and maintained after gastrulation in the embryonic tailbud, 2) the mechanism by which the canonical Wnt signaling pathway induces mesoderm within axial stem cells, and 3) how the Sox2 transcription factor promotes neural induction in axial stem cells.