Grant: Project Grant

Fish fins and limbs of mammals evolved from similar structures. Fish have kept the ability to regenerate their fins after injury and to re-develop bony rays that were lost. Regeneration depends on the formation of a group of proliferative and undifferentiated cells which will progressively differentiate as the regenerate is growing. One important question to address mechanisms of regeneration is to determine how interactions between cells allow the regeneration process. Fin rays are made of a series of bone segments separated by joints. We are interested in understanding how these bone segments and joints are regularly added at the tip of the ray as the fin regenerates. We showed that bone cells (osteoblasts) and joint cells come from the same precursor cells. Our first hypothesis is that changes in the level of gene expression or activation of others is informing the precursor to form a joint cell or an osteoblast. Osteoblast maturation follows a step by step program. We recently identified osteoblasts expressing a combination of genes indicating that this osteoblast population represents a new ''step'' in the maturation program. Our second hypothesis is that the presence of this new osteoblast population depends on interactions with adjacent cells. We propose to test our hypotheses by using techniques that allow 1) to perturb gene activity or 2) to eliminate specific cells (e.g. joint cells) to examine the impact on bone and joint formation and on the regeneration process in general. This work will allow to better understand how cells communicate to assure the formation of new bone and of joints between these bones. The relative simplicity of the fin regenerate make it an excellent model to study regeneration mechanisms, a fundamental knowledge that will be important in establishing strategies to develop methods, drugs or tools to induce a regeneration response to injury, trauma or degenerative event in species that do not regenerate, including humans.