Salamanders are champions at regenerating lost body parts. A flatworm called a planarian can grow back its entire body from a speck of tissue, but it is a very small, simple creature. Zebra fish can regrow their tails throughout their lives. Humans, along with other mammals, can regenerate lost limb buds as embryos. As young children, we can regrow our fingertips; mice can still do this as adults. But salamanders stand out as the only vertebrates that can replace complex body parts that are lost at any age, which is why researchers seeking answers about regeneration have so often turned to them.
While researchers studying animals like mice and flies progressed into the genomic age, however, those working on axolotls were left behind. One obstacle was that axolotls live longer and mature more slowly than most lab animals, which makes them cumbersome subjects for genetics experiments. Worse, the axolotl’s enormous and repetitive genome stubbornly resisted sequencing.
Then a European research team overcame the hurdles and finally published a full genetic sequence for the laboratory axolotl earlier this year. That accomplishment could change everything.
“The genome was a huge problem that had been lingering over the heads of everyone working in axolotl,” said Jessica Whited, the assistant professor and researcher who supervises this laboratory at Harvard Medical School and Brigham and Women’s Hospital. Now that she and other researchers have the whole axolotl genome, they’re hoping to unlock secrets of regeneration and perhaps even to learn how humans could harness this power for ourselves
After an amputation, a salamander bleeds very little and seals off the wound within hours. Cells then migrate to the wound site and form a blob called a blastema. Most of these recruits seem to be cells from nearby that have turned back their own internal clocks to an unspecialized or “dedifferentiated” state more like that seen in embryos. But it’s unclear whether and to what extent the animal also calls on reserves of stem cells, the class of undifferentiated cells that organisms maintain to help with healing. Whatever their origin, the blastema cells redifferentiate into new bone, muscle and other tissues. A perfect new limb forms in miniature, then enlarges to the exact right size for its owner.
Scientists don’t know whether axolotls use the same mechanisms to regenerate their internal organs as their limbs. They also don’t know why an axolotl can grow back an arm many times in a row but not indefinitely — after being amputated five times, most axolotl limbs stop coming back. Another mystery is how a limb knows to stop growing when it reaches the right size.
Monaghan is studying axolotl retinas to try to improve the outcomes of prospective stem cell therapies in aging human eyes. He also thinks finding out how axolotls rapidly regrow their lungs could help us learn to heal human lungs, which naturally have some regenerative power.
McCusker has studied how the tissue environment of a salamander’s regenerating limb controls the behavior of cells. Someday, we might be able to regulate the environment around a cancer cell and force it to behave normally.