Understanding the cellular and molecular mechanisms of fingertip (digit tip) regeneration in mammals.

Approximately two million people in North America are living with lower limb loss, caused predominantly from complications of diabetes, peripheral vascular disease, trauma and cancer. The ability to regenerate an organ varies widely across the animal kingdom; while amphibians can regenerate entire limbs, 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). In mammals including humans, the fingertip will regenerate completely and appropriately as long as the base of the nail (or nail bed) is still intact or else lead to 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 what controls the decision to regenerate or to form a scar. Similarities with human fingertip injury responses make our system one of the most clinically relevant models of tissue regeneration in a mammal. My proposed study will explore how the nail bed creates an environment enabling regeneration rather than scar formation, and will identify the soluble signals from the nail bed that communicate with other stem cells that ensures the generation of a new fingertip.