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:GSE213435, GEO:GSE193501, GEO:GSE193503, GEO:GSE193502, GEO:GSE198098
- 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
- PubMed
- 37567873 Full text @ Nat. Commun.
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.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping