Schwann Cell Role in Selectivity of Nerve Regeneration

Cells. 2020 Sep 20;9(9):2131. doi: 10.3390/cells9092131.

Abstract

Peripheral nerve injuries result in the loss of the motor, sensory and autonomic functions of the denervated segments of the body. Neurons can regenerate after peripheral axotomy, but inaccuracy in reinnervation causes a permanent loss of function that impairs complete recovery. Thus, understanding how regenerating axons respond to their environment and direct their growth is essential to improve the functional outcome of patients with nerve lesions. Schwann cells (SCs) play a crucial role in the regeneration process, but little is known about their contribution to specific reinnervation. Here, we review the mechanisms by which SCs can differentially influence the regeneration of motor and sensory axons. Mature SCs express modality-specific phenotypes that have been associated with the promotion of selective regeneration. These include molecular markers, such as L2/HNK-1 carbohydrate, which is differentially expressed in motor and sensory SCs, or the neurotrophic profile after denervation, which differs remarkably between SC modalities. Other important factors include several molecules implicated in axon-SC interaction. This cell-cell communication through adhesion (e.g., polysialic acid) and inhibitory molecules (e.g., MAG) contributes to guiding growing axons to their targets. As many of these factors can be modulated, further research will allow the design of new strategies to improve functional recovery after peripheral nerve injuries.

Keywords: Schwann cell; axon; axon-glia interactions; motor; peripheral nerve injury; preferential motor reinnervation; regeneration; reinnervation accuracy; sensory.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Axons / metabolism*
  • Biomarkers / metabolism
  • Cell Adhesion
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cell Communication
  • Gene Expression
  • Humans
  • Myelin Basic Protein / genetics
  • Myelin Basic Protein / metabolism
  • Nerve Regeneration / physiology*
  • Peripheral Nerve Injuries / genetics*
  • Peripheral Nerve Injuries / metabolism
  • Peripheral Nerve Injuries / pathology
  • Phenotype
  • Recovery of Function / physiology*
  • Schwann Cells / metabolism*
  • Schwann Cells / pathology
  • Sialic Acids / metabolism

Substances

  • Biomarkers
  • Cell Adhesion Molecules, Neuronal
  • Myelin Basic Protein
  • Sialic Acids
  • neuroligin 1
  • polysialic acid