Investigating Nrg1 Signaling in the Regenerating Axolotl Spinal Cord Using Multiplexed FISH

Abstract

Amputation of a salamander tail leadsto functional spinal cord regeneration through activation of endogenous stem cells. Identifying the signaling pathways that control cell proliferation in these neural stem cells will help elucidate the mechanisms underlying the salamander's regenerative ability. Here, we show that neuregulin 1 (Nrg1)/ErbB2 signaling is an important pathway in the regulation of neural stem cell proliferation in the spinal cord of the axolotl salamander (Ambystoma mexicanum ). Simultaneous localization of nrg1 mRNA and Nrg1 protein was performed by utilizing a hybridization chain reaction fluorescence in situ hybridization (FISH) methodology in tissue sections. Multiplexed FISH also permitted the phenotyping of multiple cell types on a single fixed section allowing the characterization of mRNA expression, protein expression, and tissue architecture. Pharmacological inhibition of ErbB2 showed that intact Nrg1/ErbB2 signaling is critical for adult homeostatic regeneration as well as for injury-induced spinal cord regeneration. Overall, our results highlight the importance of the NRG1/ErbB2 signaling pathway in neural stem cell proliferation in the axolotl.

Adult Neural Stem Cells in Development, Regeneration, and Aging

“…The Neuregulin 1/ErbB2 signaling pathway is known to play an important part in development of the nervous system, and increasing evidence suggests that it contributes to the recovery of mammalian spinal cord injury (Guo et al , ; Mei and Nave, ; Jing et al , ). As an effort to elucidate the role of Neuregulin 1 and its receptor ErbB2 in stem cell‐mediated regeneration, Freitas et al () describe in this Special Issue their research on the role of this molecular signaling in development and repair of the axolotl spinal cord. They show that intact Neuregulin 1/ErbB2 signaling is necessary for spinal cord regeneration in this species.…”