Cellular and molecular mechanisms of axolotl central and peripheral nervous system response to injury

The axolotl (Ambystoma mexicanum) is one of the only known tetrapod vertebrates capable of full spinal cord regeneration. Unfortunately, similar injury in mammals is completely debilitating, as it permanently forms a glial scar, which prevents regeneration. Therefore, the axolotl is an indispensable model for the study of the molecular pathways underlying regenerative abilities. Similarly, axolotls are capable of extensive axonal regeneration which plays an invaluable role in regenerating a full appendage. Our work focuses on uncovering cellular and molecular pathways underlying nervous system regeneration. Among them is discovering the functional role of Neuregulin 1 (NRG1) during adult neurogenesis and spinal cord regeneration after injury. Specifically, we find that pharmacological inhibition of NRG1 signaling prevents axolotl tail and spinal cord regeneration. Animals treated with the NRG1 receptor inhibitor Mubritinib did not fully regenerate their tails and had structurally abnormal spinal cord compared to control animals, which could be due to reduced neurogenesis exhibited after drug-treatment. We have also highlighted the importance of NRG1 for neurogenesis during homeostasis, emphasized by the fact that NRG1 positive cells co-localize with the ependymal stem cells of the axolotl spinal cord in an uninjured animal.