TitleEnhanced Neuronal Regeneration in the CAST/Ei Mouse Strain Is Linked to Expression of Differentiation Markers after Injury.
Publication TypeJournal Article
Year of Publication2017
AuthorsLisi V, Singh B, Giroux M, Guzman E, Painter MW, Cheng Y-C, Huebner E, Coppola G, Costigan M, Woolf CJ, Kosik KS
JournalCell Rep
Date Published2017 Aug 01
KeywordsAnimals, Basic Helix-Loop-Helix Transcription Factors, Male, Mice, MicroRNAs, Nerve Regeneration, Neurites, Peripheral Nerve Injuries

Peripheral nerve regeneration after injury requires a broad program of transcriptional changes. We investigated the basis for the enhanced nerve regenerative capacity of the CAST/Ei mouse strain relative to C57BL/6 mice. RNA sequencing of dorsal root ganglia (DRG) showed a CAST/Ei-specific upregulation of Ascl1 after injury. Ascl1 overexpression in DRG neurons of C57BL/6 mice enhanced their neurite outgrowth. Ascl1 is regulated by miR-7048-3p, which is downregulated in CAST/Ei mice. Inhibition of miR-7048-3p enhances neurite outgrowth. Following injury, CAST/Ei neurons largely retained their mature neuronal profile as determined by single-cell RNA- seq, whereas the C57BL/6 neurons acquired an immature profile. These findings suggest that one facet of the enhanced regenerative phenotype is preservation of neuronal identity in response to injury.

Alternate JournalCell Rep
PubMed ID28768198
PubMed Central IDPMC5565222
Grant ListP30 HD018655 / HD / NICHD NIH HHS / United States
S10 OD010610 / OD / NIH HHS / United States
U54 HD090255 / HD / NICHD NIH HHS / United States