Neuronal activation in the axolotl brain promotes tail regeneration

S E Walker; K Yu; S Burgess; K Echeverri

doi:10.1038/s41536-025-00413-2

Neuronal activation in the axolotl brain promotes tail regeneration

NPJ Regen Med. 2025 May 8;10(1):22. doi: 10.1038/s41536-025-00413-2.

Authors

S E Walker¹, K Yu², S Burgess², K Echeverri³

Affiliations

¹ Marine Biological Laboratory, Eugene Bell Center for Regenerative Biology, Woods Hole, MA, USA.
² Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
³ Marine Biological Laboratory, Eugene Bell Center for Regenerative Biology, Woods Hole, MA, USA. kecheverri@mbl.edu.

Abstract

The axolotl retains a remarkable capacity for regenerative repair and is one of the few vertebrate species capable of regenerating its brain and spinal cord after injury. To date, studies investigating axolotl spinal cord regeneration have placed particular emphasis on understanding how cells immediately adjacent to the injury site respond to damage to promote regenerative repair. How neurons outside of this immediate injury site respond to an injury remains unknown. Here, we identify a population of dpErk⁺/etv1⁺ glutamatergic neurons in the axolotl telencephalon that are activated in response to injury and are essential for tail regeneration. Furthermore, these neurons project to the hypothalamus where they upregulate the neuropeptide neurotensin in response to injury. Together, these findings identify a unique population of neurons in the axolotl brain whose activation is necessary for successful tail regeneration, and sheds light on how neurons outside of the immediate injury site respond to an injury.