Reindeer antler velvet as a model system of tissue regeneration

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Lower vertebrates such as salamanders are capable remarkable tissue regeneration, to the extent that they can regrow entire limbs following amputation. However, as mammals have evolved, this regenerative capacity has been largely diminished. How regeneration might be restored is of great interest. Deer antlers are the only mammalian organs capable of complete regeneration. The University of Calgary maintains a resource herd of captive reindeer for teaching and research thus providing a unique (mammalian) model to study tissue regeneration. In a series of preliminary experiments my lab discovered that the adult antler skin (called ‘velvet’) is capable of complete regeneration without forming a scar, a phenomenon only ever documented in embryonic mammalian skin. Regenerated velvet contains newly formed hair follicles and associated sebaceous glands, dense innervation and re-established pigmentation. Thus, the reindeer antler provides a powerful model system to study the basic cellular and molecular dynamics that underlie adult mammalian tissue growth and injury-induced regeneration. The objectives of this project are: 1) To identify genes that are exclusively altered during antler velvet regeneration and during scar-less wound healing. We will perform high-throughput gene expression analyses in antler velvet versus backskin (which does not regenerate). 2) To determine the functional contribution of identified genes. We will genetically delete a subset of genes to understand their importance during antler growth and/or during injury-induced regeneration. 3) To determine the influence of the local ‘antler’ environment on regenerative competence. Our work has shown that the velvet exhibits complete regeneration after injury, whilst similar wounds on backskin in the same animal form fibrotic ‘scar’, devoid of appendages or pigment. We will graft antler velvet on to the back (a non-regenerative site) and then ask whether the velvet retains its inherent regenerative capacity. 4) To determine the cellular origin of antlers. In preliminary work, we isolated a mesenchymal cell from early antler that exhibits continuous self-renewal in vitro and exhibits specific markers associated with a multipotent embryonic population called neural crest. We will isolate, characterize and subsequently transplant labeled progenitors back into the regenerating antler and then analyze their fate within the mature antler in order to understand the cellular basis for antler regeneration. Our long-term goal is to generate fundamental knowledge about how cells are directed to form organized tissues, how cell growth/proliferation is controlled and why regeneration fails in most adult mammalian tissues. Knowledge gleaned from this research program may inform future work to improve wound healing in human and veterinary medicine.