Grant: Undergraduate: Mobility, musculoskeletal health and arthritis - ICS

PI15 protein was discovered originally in brain cancer cells but since then it was also identified in the developing limbs and face of embryos. Since nothing was known about the normal function of this protein we began by introducing the PI15 gene into chicken embryos. The most dramatic effects were obtained on the skeleton. PI15 inhibited bone formation in the upper face and induced extra digits in the limbs. It is curious that one gene can have such different effects on the face and limb skeletons. While the results implied that PI15 was affecting skeletal development, it was not possible to determine whether there were direct effects on the cells that make cartilage or bone. To answer this question in the proposed study we will create high density cell cultures directly from the embryonic limb and the face and treat these with PI15 protein. A cell line has been engineered to express PI15 protein in the Richman lab and we will transfer media from these secreting cells to the micromass cultures. With normal culture conditions such high density micromass cultures will make distinct cartilage nodules surrounded by incipient bone. Here the aim is to measure the effects of PI15 on the cartilage nodule size and number, as well as whether differentiation is accelerated or delayed. We will contrast the effects on the face and the limb in order to understand the differences in responses to the gene in the embryo. These studies would be the first to analyze the role of PI15 in bone and cartilage formation. The knowledge gained from this study could one day be used to design novel therapies for treating injuries or diseases that affect the skeleton.