Localized EMT reprograms glial progenitors to promote spinal cord repair

Dev Cell. 2021 Mar 8;56(5):613-626.e7. doi: 10.1016/j.devcel.2021.01.017. Epub 2021 Feb 19.


Anti-regenerative scarring obstructs spinal cord repair in mammals and presents a major hurdle for regenerative medicine. In contrast, adult zebrafish possess specialized glial cells that spontaneously repair spinal cord injuries by forming a pro-regenerative bridge across the severed tissue. To identify the mechanisms that regulate differential regenerative capacity between mammals and zebrafish, we first defined the molecular identity of zebrafish bridging glia and then performed cross-species comparisons with mammalian glia. Our transcriptomics show that pro-regenerative zebrafish glia activate an epithelial-to-mesenchymal transition (EMT) gene program and that EMT gene expression is a major factor distinguishing mammalian and zebrafish glia. Functionally, we found that localized niches of glial progenitors undergo EMT after spinal cord injury in zebrafish and, using large-scale CRISPR-Cas9 mutagenesis, we identified the gene regulatory network that activates EMT and drives functional regeneration. Thus, non-regenerative mammalian glia lack an essential EMT-driving gene regulatory network that reprograms pro-regenerative zebrafish glia after injury.

Keywords: CRISPR/Cas9 mutagenesis; EMT; astrocytes; bridging; glia; regeneration; spinal cord injury; zebrafish.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition*
  • Mammals
  • Neuroglia / cytology*
  • Neuroglia / physiology
  • Neurons / cytology
  • Neurons / physiology
  • Spinal Cord / cytology*
  • Spinal Cord / physiology
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / therapy*
  • Spinal Cord Regeneration*
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism


  • Zebrafish Proteins