PUBLICATION

Functional Regeneration of the Sensory Root via Axonal Invasion

Authors
Nichols, E.L., Smith, C.J.
ID
ZDB-PUB-200109-7
Date
2020
Source
Cell Reports   30: 9-17.e3 (Journal)
Registered Authors
Keywords
DREZ, DRG, OBPI, actin, behavior, invasion, regeneration, spinal cord, zebrafish
MeSH Terms
  • Actins/metabolism
  • Animals
  • Axons/physiology*
  • Behavior, Animal/drug effects
  • Ganglia, Spinal/physiopathology
  • Nerve Regeneration/physiology*
  • Paclitaxel/pharmacology
  • Sensory Receptor Cells/physiology*
  • Spinal Cord/physiopathology
  • Spinal Cord Injuries/physiopathology
  • Zebrafish
PubMed
31914401 Full text @ Cell Rep.
Abstract
Regeneration following spinal root avulsion is broadly unsuccessful despite the regenerative capacity of other PNS-located nerves. By combining focal laser lesioning to model root avulsion in zebrafish, time-lapse imaging, and transgenesis, we identify that regenerating DRG neurons fail to recapitulate developmental paradigms of actin-based invasion after injury. We demonstrate that inducing actin reorganization into invasive components via pharmacological and genetic approaches in the regenerating axon can rescue sensory axon spinal cord entry. Cell-autonomous induction of invasion components using constitutively active Src induces DRG axon regeneration, suggesting an intrinsic mechanism can be activated to drive regeneration. Furthermore, analyses of neuronal activity and animal behavior show restoration of sensory circuit activity and behavior upon stimulating axons to re-enter the spinal cord via invasion. Altogether, our data identify induction of invasive components as sufficient for functional sensory root regeneration after injury.
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