The Astonishing Ability of Salamanders to Regrow Limbs

For many creatures, losing a limb is a permanent condition. However, salamanders, especially axolotls, possess an extraordinary ability: they can regenerate entire limbs in as little as six weeks. Furthermore, they can also regenerate heart and even brain tissue. How does this remarkable adaptation work?

The Development of Limbs

Regardless of regeneration, every limbed creature must develop its arms and legs at some point. This process typically begins with small bumps called limb buds, whether it starts in the womb or after birth. These buds are filled with progenitor cells, which can differentiate into various tissues, including:

• Muscles
• Cartilage
• Ligaments
• Tendons

Some of these progenitors are stem cells, capable of developing into a range of specialized cells and tissues, while others are derived from stem cells. As the limb bud develops, the progenitors differentiate and multiply rapidly. Nerves grow into the limb from nearby cell bodies, and a network of blood vessels forms, providing oxygen to fuel the process. Eventually, the tiny bud grows into a full infant limb.

Salamanders' Regenerative Process

Most salamanders, including axolotls, develop their limbs in the same way. However, unlike other animals, they can restart this process if needed. When a salamander loses a limb, surrounding skin cells quickly move across the wound's surface, forming a new layer called the wound epidermis. Once established, this layer signals cells in the underlying limb stump to undergo dedifferentiation.

Dedifferentiation and Stem Cell Activation

Dedifferentiation reverts nearby cells from fully developed limb tissues back into earlier, less specialized progenitor cells. Simultaneously, the peripheral nervous system activates stem cells throughout the salamander's body. Unlike most multicellular organisms, whose stem cells lose regenerative capacity with age, salamander stem cells near the injury reactivate and start multiplying when they receive the right signal.

The Blastema: A Key Component

Researchers are still determining the exact ratio of stem cells and dedifferentiated progenitor cells required for regeneration. However, these cells come together to form the blastema, the most critical part of the process. The blastema is almost identical to a limb bud, except it is made of recycled, repurposed, and potentially reserved cells rather than entirely new ones.

Limb Regrowth

Like limb buds, blastemas have the same mission: to create thousands of new cells and organize them into the muscle, bone, skin, and nerve tissue needed for a functional limb. Nerves and blood vessels spanning the injury site transmit nutrition and oxygen as this process unfolds. Over several weeks, the stump steadily grows a miniature limb with translucent skin. When the process is complete, the limb will match the rest of the salamander, and there won't even be a scar.

Mysteries and Research

The relationship between scarring and regeneration is just one of the many mysteries surrounding this process. Scientists are still tracking salamander cells on the molecular level to understand how they revert from a mature stage into a regenerative one. Research into transplanting blastema cells is also underway to investigate how other animals might replicate this reconstructive ability.

Positional Memory and Growth Control

Scientists are also trying to understand how salamanders' bodies know what part of the limb has been lost and how much needs to be regrown. One theory suggests that blastema cells have a form of positional memory, allowing them to determine how much to grow in relation to one another. It is equally important to understand how these limbs know when to stop growing to prevent overdevelopment, as seen in cancerous tumors.

Regeneration in Other Animals

The blastema is not unique to salamanders. Deer antlers use a similar healing tissue to regenerate each year, even though their skin scars like ours. Spiny mice can also restore skin, hair, and some other appendages without scarring. Even humans can regenerate the tips of their fingers and toes in a surprisingly similar manner.

Evolutionary Connections

It remains unknown whether this ability is tied to our shared ancestry with salamanders or fueled by distinct biological mechanisms. However, with time and research, we may uncover more evolutionary knowledge and potentially unlock new regenerative capabilities.