PUBLICATION

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

Authors
Cigliola, V., Shoffner, A., Lee, N., Ou, J., Gonzalez, T.J., Hoque, J., Becker, C.J., Han, Y., Shen, G., Faw, T.D., Abd-El-Barr, M.M., Varghese, S., Asokan, A., Poss, K.D.
ID
ZDB-PUB-230813-45
Date
2023
Source
Nature communications   14: 48574857 (Journal)
Registered Authors
Becker, Clay, Cigliola, Valentina, Han, Yanchao, Lee, Nutishia, Ou, Jianhong, Poss, Kenneth D., Shoffner, Adam
Keywords
none
Datasets
GEO:GSE198098, GEO:GSE193502, GEO:GSE193501, GEO:GSE213435, GEO:GSE193503
MeSH Terms
  • Animals
  • Axons/metabolism
  • Heparin-binding EGF-like Growth Factor/genetics
  • Heparin-binding EGF-like Growth Factor/metabolism
  • Humans
  • Mammals
  • Mice
  • Nerve Regeneration/genetics
  • Spinal Cord/metabolism
  • Spinal Cord Injuries*/genetics
  • Spinal Cord Injuries*/metabolism
  • Spinal Cord Injuries*/therapy
  • Spinal Cord Regeneration*/physiology
  • Zebrafish/genetics
(all 14)
PubMed
37567873 Full text @ Nat. Commun.
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.
Genes / Markers
Marker Marker Type Name
actb1GENEactin, beta 1
adcyap1bGENEadenylate cyclase activating polypeptide 1b
ccn2aGENEcellular communication network factor 2a
en.hbegfaENHANCERhbegfa enhancer
en.ncoa4ENHANCERncoa4 enhancer
en.prp38fbENHANCERprp38fb enhancer
en.ssuh2.4ENHANCERssuh2.4 enhancer
hbegfaGENEheparin-binding EGF-like growth factor a
hbegfbGENEheparin-binding EGF-like growth factor b
hsp70lGENEheat shock cognate 70-kd protein, like
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Figures
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
bns5
    		Small Deletion
    mi2002TgTransgenic Insertion
      pd96TgTransgenic Insertion
        pd360TgTransgenic Insertion
          pd361TgTransgenic Insertion
          pd362
            		Small Deletion
            pd363
              		Small Deletion
              pd364TgTransgenic Insertion
                pd365TgTransgenic Insertion
                  pd366TgTransgenic Insertion
                    1 - 10 of 15
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                    Human Disease / Model
                    No data available
                    Sequence Targeting Reagents
                    Target Reagent Reagent Type
                    hbegfaCRISPR4-hbegfaCRISPR
                    hbegfaCRISPR5-hbegfaCRISPR
                    hbegfbCRISPR1-hbegfbCRISPR
                    hbegfbCRISPR2-hbegfbCRISPR
                    hbegfbTALEN1-hbegfbTALEN
                    1 - 5 of 5
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                    Fish
                    No data available
                    Antibodies
                    Orthology
                    Engineered Foreign Genes
                    Marker Marker Type Name
                    EGFPEFGEGFP
                    GFPEFGGFP
                    mCherryEFGmCherry
                    NTREFGNTR
                    TagBFPEFGTagBFP
                    1 - 5 of 5
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                    Mapping
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                    Citation
                    Cigliola, V., Shoffner, A., Lee, N., Ou, J., Gonzalez, T.J., Hoque, J., Becker, C.J., Han, Y., Shen, G., Faw, T.D., Abd-El-Barr, M.M., Varghese, S., Asokan, A., Poss, K.D. (2023) Spinal cord repair is modulated by the neurogenic factor Hb-egf under direction of a regeneration-associated enhancer. Nature communications. 14:48574857.