Have you ever seen a lizard regrow its tail? What if people had this ability to regrow a lost limb or organ? In the animal kingdom, anamniotes—fish and amphibians that lay eggs in aquatic environments—such as salamanders and zebrafish, have extensive regenerative properties. The axolotl is the first model for regenerative studies and has been studied since the 1860s for its ability to restore limbs, tails, eyes, and hearts [1]. Zebrafish are even capable of regenerating their brains. Lizards, on the other hand, are part of a vertebrate group known as amniotes. Amniotes include reptiles, birds, and mammals that reproduce on dryland. Surprisingly, lizards are the only amniotes capable of cell regeneration and are the closest relatives of humans that can regrow tissue [5]. They regrow their tails through autonomy, an anti-predation strategy that utilizes cell regeneration to restore damaged and lost tissue [2]. Understanding this regenerative process could be essential for regenerative medicine and treating neurological disorders.
How is regeneration possible? Neurogenesis is a process integral to tail regeneration. Neurons are generated from neural stem cells in the adult brain to add to or replace neurons in pre-existing circuits [3]. It occurs in the telencephalon, the part of the brain responsible for higher-level functions such as thinking, memory, and processing sensory information. Adult neurogenesis occurs in all vertebrate groups, including humans, but has more extensive effects in non-mammalian groups [3]. For example, neurogenesis in lizards produces more neurons and impacts more parts of the brain. In mammals, it is restricted to olfactory bulbs and the hippocampal dentate gyrus, the regions of the brain responsible for sense of smell and processing sensory information. This limitation means that while neurons are replaced in these areas, other parts of the brain are still susceptible to damage and deterioration.
Current hypotheses suggest that regeneration is a trait that occurred early in evolution, as it is most commonly found in lower-level organisms. Higher-level organisms, like humans and other mammals, evolved to have more robust immune systems with defensive macrophages— white blood cells responsible for detecting and breaking down viruses and bacteria—at the expense of regenerative capabilities [1]. These strong immune systems dispose of viral and bacterial tissue, whereas lizards and anamniotes rely on non-immune mechanisms to avoid infection [5]. Baffling to researchers, although macrophages regulate the regeneration process, macrophage depletion in salamanders and zebrafish leads to delayed or altogether halted regeneration [5].
Harnessing this ability in humans would revolutionize research and healthcare. Researchers are working to leverage the unique regenerative capabilities of lizards as a model to transform the field of regenerative medicine. They use the lizard model to reprogram somatic cells—cells found in mammals that repair or replace damaged or aging tissue—toward a multipotent state, in which they become specialized for various tissues and functions [1]. This would mean that, on a small scale, humans could restore damaged or lost tissue. Advancements in studying neurogenesis could significantly impact regenerative medicine, neuroscience, and the treatment of neurological disorders. This progress would revolutionize the future of medicine, changing the landscape for disease and disorder treatment.
References
Daponte, V., Tylzanowski, P., & Forlino, A. (2021). Appendage Regeneration in Vertebrates: What Makes This Possible? Cells, 10(2), 242. https://doi.org/10.3390/cells10020242. Most helpful connection to biomedicine.
Donato, S. V., & Vickaryous, M. K. (2022). Radial Glia and Neuronal-like Ependymal Cells Are Present within the Spinal Cord of the Trunk (Body) in the Leopard Gecko (Eublepharis macularius). Journal of Developmental Biology, 10(2), 21. https://doi.org/10.3390/jdb10020021
González-Granero, S., Font, E., Desfilis, E., Herranz-Pérez, V., & José Manuel García‐Verdugo. (2023). Adult neurogenesis in the telencephalon of the lizard Podarcis liolepis. Frontiers in Neuroscience, 17. https://doi.org/10.3389/fnins.2023.1125999
Hye Ryeong Kim, Choi, H., Soon Yong Park, Song, Y., Kim, J.-H., Shim, S.-I., Jun, W., Kim, K., Han, J., Chi, S., Sun‐Hee Leem, & Jin Woong Chung. (2022). Endoplasmin regulates differentiation of tonsil-derived mesenchymal stem cells into chondrocytes through ERK signaling. Journal of Biochemistry and Molecular Biology, 55(5), 226–231. https://doi.org/10.5483/bmbrep.2022.55.5.173
Londono, R., Tighe, S., Milnes, B., DeMoya, C., Quijano, L. M., Hudnall, M. L., Nguyen, J., Tran, E., Badylak, S., & Lozito, T. P. (2020). Single cell sequencing analysis of lizard phagocytic cell populations and their role in tail regeneration. Journal of Immunology and Regenerative Medicine, 8, 100029. https://doi.org/10.1016/j.regen.2020.100029