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
Volume20
Issue5
Pagination1136-1147
Date Published2017 Aug 01
ISSN2211-1247
KeywordsAnimals, Basic Helix-Loop-Helix Transcription Factors, Male, Mice, MicroRNAs, Nerve Regeneration, Neurites, Peripheral Nerve Injuries
Abstract

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.

DOI10.1016/j.celrep.2017.07.010
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