Advances in signaling in vertebrate regeneration as a prelude to regenerative medicine

While all animals have evolved strategies to respond to injury and disease, their ability to functionally recover from loss of or damage to organs or appendages varies widely damage to skeletal muscle, but, unlike amphibians and fish, they fail to regenerate heart, lens, retina, or appendages. The relatively young field of regenerative medicine strives to develop therapies aimed at improving regenerative processes in humans and is predicated on >40 years of success with bone marrow transplants. Further progress will be accelerated by implementing knowledge about the molecular mechanisms that regulate regenerative processes in model organisms that naturally possess the ability to regenerate organs and/or appendages. In this review we summarize the current knowledge about the signaling pathways that regulate regeneration of amphibian and fish appendages, fish heart, and mammalian liver and skeletal muscle. While the cellular mechanisms and the cell types involved in regeneration of these systems vary widely, it is evident that shared signals are involved in tissue regeneration. Signals provided by the immune system appear to act as triggers of many regenerative processes. Subsequently, pathways that are best known for their importance in regulating embryonic development, in particular fibroblast growth factor (FGF) and Wnt/beta-catenin signaling (as well as others), are required for progenitor cell formation or activation and for cell proliferation and specification leading to tissue regrowth. Experimental activation of these pathways or interference with signals that inhibit regenerative processes can augment or even trigger regeneration in certain contexts.