Mesenchymal Stem Cell Self-renewal and Differentiation Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the ability to differentiate into chondrocytes, osteoblasts, adipocytes, fibroblasts, and tenocytes depending on the combination of growth and differentiation factors received. MSCs are not only important during development, but also during the repair of injured postnatal and adult tissues. With increasing interest in the clinical use of MSCs for tissue repair, it is of critical importance to define the signaling pathways that regulate MSC self-renewal, proliferation, lineage commitment, and differentiation. In our lab, we study the regulation of MSC populations by several signaling pathways, with emphasis on the Cox-2/PGE2, Wnt/β-catenin, and Bmp/Tak1 signaling pathways. We culture primary MSCs isolated from mouse bone marrow, as well as periosteal-derived MSCs isolated from the fracture callus, to study, in vitro, the signaling mechanisms governing MSC fate. Specifically, we are exploring the use of small molecule agonists or inhibitors to affect proliferation or differentiation of MSCs in culture. Additionally, using the mouse Cre-loxP system, we are able to determine the in vivo role of genes of interest specifically in limb mesenchymal stem cells during skeletal development.