Satellite glial cell manipulation prior to axotomy enhances developing dorsal root ganglion central branch regrowth into the spinal cord

Aug 14, 2024Glia

Changing supportive cells before nerve injury may improve nerve regrowth into the spinal cord during development

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Abstract

Peripheral satellite glial cells (SGCs) may inhibit central axon regrowth in sensory neurons following injury.

SGCs relocate their nuclei to the injury site when dorsal root ganglia neurons form new central branch neurites.
Laser ablation of SGCs before axon injury leads to increased attempts at neurite growth and a higher rate of successful regrowth.
The response of SGCs to injury is partially mediated by ErbB signaling, as inhibiting this receptor reduces SGC movement.
These findings suggest that SGCs play a role in limiting the regeneration of central axons after injury.

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The central and peripheral nervous systems (CNS and PNS, respectively) exhibit remarkable diversity in the capacity to regenerate following neuronal injury with PNS injuries being much more likely to regenerate than those that occur in the CNS. Glial responses to damage greatly influence the likelihood of regeneration by either promoting or inhibiting axonal regrowth over time. However, despite our understanding of how some glial lineages participate in nerve degeneration and regeneration, less is known about the contributions of peripheral satellite glial cells (SGC) to regeneration failure following central axon branch injury of dorsal root ganglia (DRG) sensory neurons. Here, using in vivo, time-lapse imaging in larval zebrafish coupled with laser axotomy, we investigate the role of SGCs in axonal regeneration. In our studies we show that SGCs respond to injury by relocating their nuclei to the injury site during the same period that DRG neurons produce new central branch neurites. Laser ablation of SGCs prior to axon injury results in more neurite growth attempts and ultimately a higher rate of successful central axon regrowth, implicating SGCs as inhibitors of regeneration. We also demonstrate that this SGC response is mediated in part by ErbB signaling, as chemical inhibition of this receptor results in reduced SGC motility and enhanced central axon regrowth. These findings provide new insights into SGC-neuron interactions under injury conditions and how these interactions influence nervous system repair.

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Satellite glial cell manipulation prior to axotomy enhances developing dorsal root ganglion central branch regrowth into the spinal cord

Abstract

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