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Investigating Nrg1 Signaling in the Regenerating Axolotl Spinal Cord Using Multiplexed FISH
Author(s) -
Freitas Polina D.,
Lovely Alexander M.,
Monaghan James R.
Publication year - 2019
Publication title -
developmental neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.716
H-Index - 129
eISSN - 1932-846X
pISSN - 1932-8451
DOI - 10.1002/dneu.22670
Subject(s) - axolotl , biology , ambystoma mexicanum , neural stem cell , microbiology and biotechnology , regeneration (biology) , spinal cord , zebrafish , spinal cord injury , stem cell , neuregulin , neuregulin 1 , neuroscience , signal transduction , genetics , gene
Amputation of a salamander tail leads to 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.