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Spinal cord repair is modulated by the neurogenic factor Hb-egf under direction of a regeneration-associated enhancer

Author

Listed:
  • Valentina Cigliola

    (Duke University
    Duke University Medical Center
    Université Côte d’Azur, Inserm, CNRS, Institut de Biologie Valrose)

  • Adam Shoffner

    (Duke University
    Duke University Medical Center
    Duke University Medical Center)

  • Nutishia Lee

    (Duke University
    Duke University Medical Center)

  • Jianhong Ou

    (Duke University
    Duke University Medical Center)

  • Trevor J. Gonzalez

    (Duke University School of Medicine)

  • Jiaul Hoque

    (Duke University School of Medicine)

  • Clayton J. Becker

    (Duke University
    Duke University Medical Center)

  • Yanchao Han

    (Soochow University)

  • Grace Shen

    (Duke University
    Duke University Medical Center)

  • Timothy D. Faw

    (Duke University
    Duke University School of Medicine
    Duke University)

  • Muhammad M. Abd-El-Barr

    (Duke University Medical Center)

  • Shyni Varghese

    (Duke University School of Medicine
    Duke University
    Duke University)

  • Aravind Asokan

    (Duke University
    Duke University Medical Center
    Duke University School of Medicine
    Duke University)

  • Kenneth D. Poss

    (Duke University
    Duke University Medical Center)

Abstract

Unlike adult mammals, zebrafish regenerate spinal cord tissue and recover locomotor ability after a paralyzing injury. Here, we find that ependymal cells in zebrafish spinal cords produce the neurogenic factor Hb-egfa upon transection injury. Animals with hb-egfa mutations display defective swim capacity, axon crossing, and tissue bridging after spinal cord transection, associated with disrupted indicators of neuron production. Local recombinant human HB-EGF delivery alters ependymal cell cycling and tissue bridging, enhancing functional regeneration. Epigenetic profiling reveals a tissue regeneration enhancer element (TREE) linked to hb-egfa that directs gene expression in spinal cord injuries. Systemically delivered recombinant AAVs containing this zebrafish TREE target gene expression to crush injuries of neonatal, but not adult, murine spinal cords. Moreover, enhancer-based HB-EGF delivery by AAV administration improves axon densities after crush injury in neonatal cords. Our results identify Hb-egf as a neurogenic factor necessary for innate spinal cord regeneration and suggest strategies to improve spinal cord repair in mammals.

Suggested Citation

  • Valentina Cigliola & Adam Shoffner & Nutishia Lee & Jianhong Ou & Trevor J. Gonzalez & Jiaul Hoque & Clayton J. Becker & Yanchao Han & Grace Shen & Timothy D. Faw & Muhammad M. Abd-El-Barr & Shyni Var, 2023. "Spinal cord repair is modulated by the neurogenic factor Hb-egf under direction of a regeneration-associated enhancer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40486-5
    DOI: 10.1038/s41467-023-40486-5
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