Axolotls Can Regrow Their Brains. Scientists Are Still Figuring Out How to Copy It.

In a laboratory at the University of Minnesota in 2013, researcher Stephane Bhatt and colleagues removed a portion of an axolotl’s brain — specifically part of the telencephalon, the region responsible for learning and memory. and watched what happened next. Within weeks, the tissue had regrown. The neurons had reconnected. The axolotl’s behavior returned to normal.

This was not a surprise to researchers who study Ambystoma mexicanum. It was a confirmation of what had been observed repeatedly since the axolotl became a laboratory animal in the nineteenth century. The axolotl can regenerate its spinal cord, its heart, its limbs, its eyes, and significant portions of its brain with a completeness and fidelity that no other vertebrate approaches. A limb removed at the shoulder regrows with the correct number of fingers, the correct bone structure, the correct musculature, and functional nerve connections, typically within a few months.

The axolotl is not the only animal capable of regeneration. Planarian flatworms can regrow their entire bodies from a fragment. Zebrafish can regenerate heart tissue. Salamanders generally have better regenerative capacity than most vertebrates. But the axolotl’s regenerative ability is the most extensive documented in any vertebrate, and it operates across a wider range of tissue types than any comparable animal.

Neoteny and the Permanent Larva

The axolotl’s biology is unusual in a second, entirely separate way. It is neotenic, meaning it retains larval characteristics into sexual maturity and never undergoes the metamorphosis that transforms other salamanders into terrestrial adults. An adult axolotl looks like a larval salamander — it keeps its external gills, its tail fin, and its aquatic lifestyle permanently. It reproduces in this larval form without ever becoming the land-dwelling adult that its developmental program would otherwise produce.

Neoteny in the axolotl is driven by low levels of thyroid hormone. If axolotls are treated with thyroid hormone or iodine, they undergo metamorphosis and transform into terrestrial salamanders that resemble their closest relative, the tiger salamander Ambystoma tigrinum. The metamorphosis is possible. The axolotl simply never triggers it under natural conditions.

Researcher Randal Voss at the University of Kentucky has studied axolotl genetics and development extensively, sequencing the axolotl genome. at 32 billion base pairs, one of the largest genomes ever sequenced. and identifying genes associated with both neoteny and regeneration. His work has shown that the regenerative capacity is linked to the axolotl’s unusual developmental state, with the retained larval characteristics associated with a cellular environment more permissive to regeneration than that of metamorphosed adults.

Lake Xochimilco and the Edge of Extinction

Ambystoma mexicanum is native to a single location on Earth: the lake complex of Xochimilco on the southern edge of Mexico City. The original lake system, which once covered much of the Valley of Mexico, has been reduced to a network of canals and small lakes by centuries of drainage and urban development. The wild axolotl population, once abundant enough to be a food source for the Aztec civilization, is now Critically Endangered, with surveys by researcher Luis Zambrano at the National Autonomous University of Mexico finding densities as low as 35 individuals per square kilometer in the remaining habitat, down from 6,000 per square kilometer in 1998.

The threats are multiple and compounding. Introduced tilapia and carp compete with axolotls for food and prey on their eggs and juveniles. Water quality in the Xochimilco canals is severely degraded by agricultural runoff and urban wastewater. The remaining habitat is fragmented and shrinking.

The axolotl that exists in laboratories around the world, the animal whose regenerative biology has been studied for 150 years, is descended from a small number of individuals exported to Europe in 1864. The wild population that those laboratory animals came from is now on the edge of disappearing entirely. The animal that can regrow its own brain cannot regrow its habitat.