Lindsay A. Dawson

My research is primarily focused on using the adult mouse digit as a model for mammalian bone, cartilage, and associated soft tissue regeneration. Successful epimorphic mammalian regeneration is restricted to amputations transecting the distal region of the digit tip, the terminal phalanx (P3). Amputation of the adjacent skeletal element, the middle phalanx (P2), has emerged as a model system to investigate regenerative failure and serves as a site to test approaches aimed at stimulating regeneration. We discovered that P2 amputation initiates a dynamic tissue repair response analogous to the proximal bone fragment of fracture healing, and identified the periosteal tissue, the cell rich outer layer of the bone, is required for the dynamic repair response post P2 amputation. Since we determined that periosteal cells are required for the P2 amputation healing response, we aimed to experimentally enhance their function into a robust regeneration response. We demonstrated that treating the P2 amputation wound with bone morphogenetic protein 2 (BMP2) targets the injured periosteal tissue and induces robust P2 regeneration, resulting in restoration of amputated skeletal length, pattern formation, and associated soft tissue regeneration. Other ongoing studies focus on the investigation of the periosteal contribution to P3 regeneration, and identifying potential differences between the P3 and P2 periosteum that may distinguish regeneration from regenerative failure.