Perineurial Glial Plasticity and the Role of TGF-β in the Development of the Blood-Nerve-Barrier

Morris, A.D., Lewis, G.M., Kucenas, S.
The Journal of neuroscience : the official journal of the Society for Neuroscience   37(18): 4790-4807 (Journal)
Registered Authors
Kucenas, Sarah, Morris, Angie
development, myelinating glia, perineurium, regeneration, zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Blood-Brain Barrier/cytology
  • Blood-Brain Barrier/embryology*
  • Blood-Brain Barrier/physiology
  • Neurogenesis/physiology
  • Neuroglia/cytology
  • Neuroglia/physiology*
  • Neuronal Plasticity/physiology*
  • Peripheral Nerves/cytology
  • Peripheral Nerves/embryology*
  • Peripheral Nerves/metabolism*
  • Transforming Growth Factor beta/metabolism*
  • Zebrafish
  • Zebrafish Proteins
28389474 Full text @ J. Neurosci.

Precisely orchestrated interactions between spinal motor axons and their ensheathing glia are vital for forming and maintaining functional spinal motor nerves. Following perturbations to peripheral myelinating glial cells, centrally-derived oligodendrocyte progenitor cells (OPCs) ectopically exit the spinal cord and myelinate peripheral nerves in myelin with central nervous system (CNS) characteristics. However, whether remaining peripheral ensheathing glia, such as perineurial glia, properly encase the motor nerve despite this change in glial cell and myelin composition, remains unknown. Using zebrafish mutants in which OPCs migrate out of the spinal cord and myelinate peripheral motor axons, we assayed perineurial glial development, maturation and response to injury. Surprisingly, in the presence of OPCs, perineurial glia exited the CNS normally. However, aspects of their development, response to injury and function were altered when compared to wildtype larvae. In an effort to better understand the plasticity of perineurial glia in response to myelin perturbations, we identified transforming growth factor beta 1 (TGF-β1) as a partial mediator of perineurial glial development. Taken together, these results demonstrate the incredible plasticity of perineurial glia in the presence of myelin perturbations.

SIGNIFICANCE STATEMENT Peripheral neuropathies can result from damage or dysregulation of the insulating myelin sheath surrounding spinal motor axons, causing pain, inefficient nerve conduction and the ectopic migration of oligodendrocyte progenitor cells (OPCs), the resident myelinating glial cell of the central nervous system (CNS), into the periphery. How perineurial glia, the ensheathing cells that form the protective blood-nerve-barrier (BNB), are impacted by this myelin composition change is unknown. Here, we report that certain aspects of perineurial glial development and injury responses are mostly unaffected in the presence of ectopic OPCs. However, perineurial glial function is disrupted along nerves containing centrally-derived myelin, demonstrating that although perineurial glial cells display plasticity despite myelin perturbations, the blood-nerve-barrier is compromised in the presence of ectopic OPCs.

Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes