Limb regeneration (top) and growth (bottom) in the Mexican axolotl. The limb on the bottom has not been injured, so the regenerating limb, on the top, has to ‘catch up’ in size. Image credit: Kaylee Wells (CC BY 4.0)
Humans’ ability to regrow lost or damaged body parts is relatively limited, but some animals, such as the axolotl (a Mexican salamander), can regenerate complex body parts, like legs, many times over their lives. Studying regeneration in these animals could help researchers enhance humans’ abilities to heal. One way to do this is using the Accessory Limb Model (ALM), where scientists wound an axolotl’s leg, and study the additional leg that grows from the wound.
The first stage of limb regeneration creates a new leg that has the right structure and shape. The new leg is very small so the next phase involves growing the leg until its size matches the rest of the animal. This phase must be controlled so that the limb stops growing when it reaches the right size, but how this regulation works is unclear. Previous research suggests that the number of nerves in the new leg could be important.
Wells et al. used a ALM to study how the size of regenerating limbs is controlled. They found that changing the number of nerves connected to the new leg altered its size, with more nerves leading to a larger leg. Next, Wells et al. created a system that used transplanted nerve bundles of different sizes to grow new legs in different sized axolotls. This showed that the size of the resulting leg is controlled by the number of nerves connecting it to the CNS. Wells et al. also showed that nerves can only control regeneration if they remain connected to the central nervous system.
These results explain how size is controlled during limb regeneration in axolotls, highlighting the fact that regrowth is directly controlled by the number of nerves connected to a regenerating leg. Much more work is needed to reveal the details of this process and the signals nerves use to control growth. It will also be important to determine whether this control system is exclusive to axolotls, or whether other animals also use it.
