At a Glance
- Researchers discovered why rabbits regrow ear tissue while mice form scars, revealing that the ability for complex regeneration may be suppressed rather than permanently lost in certain mammals.
- Using advanced cellular analysis, scientists identified a key chemical pathway involving retinoic acid, which was highly active in regenerating rabbits but almost absent in nonregenerating mice.
- The regeneration failure in mice was caused by the low activity of the Aldh1a2 enzyme, which prevented the necessary production of retinoic acid to direct tissue regrowth after injury.
- Scientists have successfully triggered ear regeneration in ordinary mice by directly applying retinoic acid to their wounds or by inserting the active gene from rabbits that switches on its production.
- The findings suggest many mammals retain a dormant capacity for regeneration, offering a new strategy for medical therapies that promote healing by reactivating these ancient genetic pathways.
Researchers have identified a dormant genetic switch that, when reactivated, enables mice to regenerate damaged ear tissue—a feat typically lost in most mammals. While animals like salamanders are renowned for regrowing entire limbs, mammals typically form scar tissue rather than regenerating complex structures. A new study published in the journal Science reveals that this lost ability may not be gone, but turned off. By comparing rabbits, which can fully regrow holes in their ears, to non-regenerating mice and rats, scientists have identified a single chemical pathway as the critical missing link.
To uncover this lost ability, an international team performed a detailed comparison of the healing process in rabbits and mice at a cellular level. Using advanced techniques like single-cell sequencing, which maps gene activity within individual cells, they analyzed the response to injury in the ear pinna, or outer ear. The analysis focused on specialized cells called wound-induced fibroblasts, which play a crucial role in repairing and rebuilding tissue. In rabbits, these fibroblasts increased production of retinoic acid, a molecule derived from vitamin A that serves as a crucial signal for growth and development. In mice, however, this chemical response was almost absent due to low activity of a key enzyme, Aldh1a2.
The team confirmed its findings through two decisive experiments. First, researchers applied retinoic acid directly to the ear wounds of ordinary mice. The treatment was successful, prompting the mice to regenerate the missing cartilage, skin, and other tissues, rather than forming a scar. Second, in a more targeted genetic approach, they identified the specific regulatory element, or enhancer, that activates the gene for the Aldh1a2 enzyme in rabbits after an injury. By creating transgenic mice that carry this single rabbit enhancer, researchers were able to activate the dormant regenerative mechanism, prompting the mice to regrow their ear structures after injury.
This discovery suggests that the genetic blueprint for regeneration may be conserved across mammals but has been silenced in many species over evolutionary time, possibly as a trade-off for faster wound healing through scarring. The findings provide a potential framework for regenerative medicine, proposing that stimulating the retinoic acid pathway could be a powerful strategy for promoting tissue regrowth in organs that do not normally regenerate. As retinoic acid is already known to play a role in bone, skin, and nerve repair, modulating its activity could unlock dormant healing capacities and inspire new therapies for a wide range of injuries.
References
- Jackson, J. & Phys.org. (2025, June 30). Switching on a silent gene revives tissue regeneration in mice. Phys.Org; Phys.org. https://phys.org/news/2025-06-silent-gene-revives-tissue-regeneration.html
- Lin, W., Jia, X., Shi, X., He, Q., Zhang, P., Zhang, X., Zhang, L., Wu, M., Ren, T., Liu, Y., Deng, H., Li, Y., Liu, S., Huang, S., Kang, J., Luo, J., Deng, Z., & Wang, W. (2025). Reactivation of mammalian regeneration by turning on an evolutionarily disabled genetic switch. Science, 388(6754), eadp0176. https://doi.org/10.1126/science.adp0176
