RT Journal Article
SR Electronic
T1 Localized activation of ependymal progenitors induces EMT-mediated glial bridging after spinal cord injury
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.02.18.955401
DO 10.1101/2020.02.18.955401
A1 Lili Zhou
A1 Brooke Burris
A1 Ryan Mcadow
A1 Mayssa H. Mokalled
YR 2020
UL http://biorxiv.org/content/early/2020/02/19/2020.02.18.955401.abstract
AB Unlike mammals, adult zebrafish undergo spontaneous recovery after major spinal cord injury. Whereas scarring presents a roadblock for mammalian spinal cord repair, glial cells in zebrafish form a bridge across severed spinal cord tissue to facilitate regeneration. Here, we performed FACS sorting and genome-wide profiling to determine the transcriptional identity of purified bridging glia. We found that Yap-Ctgf signaling activates epithelial to mesenchymal transition (EMT) in localized niches of ependymal cells to promote glial bridging and regeneration. Preferentially activated in early bridging glia, Yap is required for the expression of the glial bridging factor Ctgfa and for functional spinal cord repair. Ctgfa regulation is controlled by an injury responsive enhancer element that drives expression in early bridging glia after injury. Yap-Ctgf signaling activates a mesenchymal transcriptional program that drives glial bridging. This study revealed the molecular signatures of bridging glia and identified an injury responsive gene regulatory network that promotes spinal cord regeneration in zebrafish.