Project 450738

The finding that some animals can regenerate lost body parts has fascinated scientists for centuries. However, the ability to regenerate varies widely; some amphibians can regenerate entire limbs, while mammals have largely lost this ability. One exception to this rule is the tip of the finger (or digit tip in mice, the model system studied here). Under the right circumstances the fingertip will regenerate completely appropriately, even in adult humans, as long as the base of the nail is still intact. By contrast, if the injury is only slightly further down the finger, and the nail is completely lost, then there is no regeneration, but only scar formation. In this proposal, we will study adult mice to ask why this one small part of the body has retained the capacity to regenerate, and will ask what controls the decision to regenerate or to form a scar, with a particular focus on the environment. We will also ask how the immune system and inflammation impact the decision to regenerate or scar, since these have been implicated in pathological scarring/fibrosis. Ultimately, it is our goal to use this information to enhance tissue repair, and to inhibit the pathological scarring and fibrosis that can cause organ failure.