RT Journal Article
SR Electronic
T1 Enhanced neuronal regeneration in the CAST/Ei mouse strain is linked to expression of differentiation markers after injury
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 160366
DO 10.1101/160366
A1 Lisi, Véronique
A1 Singh, Bhagat
A1 Giroux, Michel
A1 Guzman, Elmer
A1 Painter, Michio W
A1 Cheng, Yung-Chih
A1 Huebner, Eric
A1 Coppola, Giovanni
A1 Costigan, Michael
A1 Woolf, Clifford J.
A1 Kosik, Kenneth S
YR 2017
UL http://biorxiv.org/content/early/2017/07/06/160366.abstract
AB 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 C57BL/6 mice DRG neurons enhanced their neurite outgrowth. Ascl1 is regulated by miR-7048-3p, which is down-regulated 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 RNAseq, 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.