Increasingly more studies of nontraditional vertebrate model organisms with extraordinary regenerative capacities are providing valuable insight into the mechanisms of complex tissue regeneration. For example, the zebrafish (Danio rerio) can regenerate many tissues after injury including cardiac, fin appendages and spinal cord. Another ray-finned fish, the bichir (Polypterus senegalus) can also regenerate cardiac and fin appendages. Urodeles (salamanders and newts), such as the axolotl (Ambystoma mexicanum), can regenerate whole limbs. Studies of models with robust regenerative capacities have advanced our understanding of regenerative mechanisms by identifying genes that are necessary and sufficient for regeneration in vivo.
Regenerative biology has historically focused on defining the cellular and molecular mechanisms within individual species. Within the last 15 years, rapid advances in genome sequencing technology and gene editing strategies have advanced the understanding of the molecular and cellular processes that define tissue regeneration. Unfortunately, they have also unintentionally created silos that encase individual animal models and discourage examination of regenerative capacity in nontraditional model systems.
Tissue regeneration is a tightly regulated complex process that involves reprogramming of differentiated tissues into highly proliferative cells. Comparisons of equivalent stages of regeneration in multiple models offer the potential to identify conserved regulatory mechanisms that enable regeneration and contrast them with models that do not regenerate. Small molecules can then be developed to reactivate these proregenerative mechanisms to potentially augment limited human regenerative capacity. Such comparative and subsequent therapeutic studies would be greatly enhanced by making critical investments to create the genetic and molecular tools to study these nontraditional models as we have done for major model organisms such as the mouse.