Regulation of mesodermal progenitors in transgenic zebrafish

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DESCRIPTION (provided by applicant): A large body of evidence in vertebrates shows that the development of the anterior trunk and the rest of the body are differentially regulated. Previous studies using mutants, knockouts, morpholinos and mRNA injection have provided very important information on the role of signaling and transcription factors in establishing the embryonic vertebrate body plan during the early gastrula stages. However, because alterations in the patterning of the early gastrula embryo cause such severe embryological defects, it has been difficult to study later stages when most of the body develops. Using transgenic lines containing heat-shock inducible cell autonomous regulators of signaling and transcription, together with a new transgenic line we developed that allows us to temporally and specifically label the mesodermal progenitors, we now have the ability to determine how the mesodermal progenitors are regulated by signaling and T-box transcription factors to progressively differentiate during somitogenesis, a process that is essential for forming a normal body and is conserved in all vertebrates. The studies described here take advantage of the ability in zebrafish to analyze the mesodermal progenitors at the single-cell level in living embryos, using cell transplants to study experimentally cell-autonomously perturbed cells within a normal background. This novel approach will allow us to examine cell behaviors that are obscured when all of the embryonic cells have alterations in signaling or transcription. Studies, particularly in mammals, show that the mesodermal progenitors are a stem-cell like population, which normally has a defined lifetime. With recent advances in the technology to produce transgenic lines, combined with the ability to study progenitors in living embryos using fluorescent reporters, zebrafish provides an excellent model system for understanding how vertebrate stem cells are regulated in vivo. As stem cells have great promise for the treatment of many diseases, the studies described here will provide valuable information about the signaling networks and transcription factors that control stem cell maintenance and tissue formation. Studies, particularly in mammals, show that the mesodermal progenitors are a stem-cell like population, which normally has a defined lifetime. With recent advances in the technology to produce transgenic lines, combined with the ability to study progenitors in living embryos using fluorescent reporters, zebrafish provides an excellent model system for understanding how vertebrate stem cells are regulated in vivo. As stem cells have great promise for the treatment of many diseases, the studies described here will provide valuable information about the signaling networks and transcription factors that control stem cell maintenance and tissue formation.