Bridging the regeneration gap: genetic insights from diverse animal models

Key Points Regeneration is widely distributed among the various phyla that compose the animal kingdom, including vertebrates. Limitations in the ability to interrogate this attribute at the molecular level have hampered efforts to delineate the mechanistic underpinnings of regeneration. Loss-of-function screens (using RNAi) and gain-of-function assays (transgenesis) have recently been introduced to study molecular pathways in traditional model systems of regeneration, overcoming past limitations to probe their biology at the molecular level. Studies in simple animals such as hydra and planarians are beginning to contribute to our understanding of tissue remodelling and adult somatic stem-cell regulation in animals. Studies in mammals and other vertebrates have highlighted central roles for the activation of specific signalling pathways in the processes of organ and limb regeneration. Comparative studies of regenerative processes among the various animals that are currently under investigation could provide important insights into the permissive and non-permissive mechanisms that underlie regenerative competence. Such information is likely to yield fundamental insights for our understanding of metazoan biology, and to expand the repertoire of therapeutic possibilities in the fields of regenerative medicine. Studies of regenerative biology have been hampered by a lack of tools for testing gene function in traditional model species. Recent advances have overcome this problem, leading to new insights into both basic regenerative biology and its biomedical potential. Significant progress has recently been made in our understanding of animal regenerative biology, spurred on by the use of a wider range of model organisms and an increasing ability to use genetic tools in traditional models of regeneration. This progress has begun to delineate differences and similarities in the regenerative capabilities and mechanisms among diverse animal species, and to address some of the key questions about the molecular and cell biology of regeneration. Our expanding knowledge in these areas not only provides insights into animal biology in general, but also has important implications for regenerative medicine and stem-cell biology.