Transforming growth factor-β blocks myelination but not ensheathment of axons by Schwann cells in vitro

V. Guenard, Lisa A Gwynn, Patrick Wood

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Mechanisms regulating Schwann cell differentiation into a myelinating or a mature nonmyelinating phenotype during development are poorly understood. Humoral factors such as members of the transforming growth factor-β (TGF- β) family, which are found in the developing and adult mammalian nervous system and are known to affect cell differentiation, could be involved. We tested the effects of TGF-β isoforms on the ensheathment and myelination of dorsal root ganglion (DRG) neurons by Schwann cells in vitro. Rat embryonic DRG neurons and Schwann cells from the sciatic nerve were isolated, purified, and recombined. In serum-free conditions, TGF-β blocked both Schwann cell myelination and the expression of the myelin-related molecules galactocerebroside, P0, myelin-associated glycoprotein, and myelin basic protein. In contrast, the expression of molecules characteristic of mature nonmyelinating Schwann cells, including neural-cell adhesion molecule, L1, and nerve growth factor receptor, was maintained when compared to Schwann cells in nondifferentiated cultures. Notably, the expression of glial fibrillary acidic protein, which is expressed only in mature nonmyelinating Schwann cells in vivo, was increased 10-fold in our cultures by TGF-β. Electron microscopic analysis indicated that in the presence of TGF-β, basal lamina deposition by Schwann cells was slightly increased. Most importantly, many axons in TGF-β-treated cultures received ensheathment typical of mature nonmyelinated nerves. These effects of TGF-β were partially reversed by specific neutralizing anti-TGF-β antibodies. We interpret these results as evidence that TGF-β regulates Schwann cell differentiation in vitro by blocking the expression of the myelinating phenotype and promoting the development of the nonmyelinating phenotype.

Original languageEnglish
Pages (from-to)419-428
Number of pages10
JournalJournal of Neuroscience
Volume15
Issue number1 I
StatePublished - Jan 1 1995

Fingerprint

Schwann Cells
Transforming Growth Factors
Axons
Cell Differentiation
Spinal Ganglia
Phenotype
Neural Cell Adhesion Molecule L1
Myelin-Associated Glycoprotein
In Vitro Techniques
Neurons
Nerve Growth Factor Receptor
Myelin Basic Protein
Glial Fibrillary Acidic Protein
Sciatic Nerve
Myelin Sheath
Basement Membrane
Nervous System
Protein Isoforms
Electrons
Antibodies

Keywords

  • differentiation
  • myelination
  • neuron
  • Schwann cell
  • transforming growth factor-β

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Transforming growth factor-β blocks myelination but not ensheathment of axons by Schwann cells in vitro. / Guenard, V.; Gwynn, Lisa A; Wood, Patrick.

In: Journal of Neuroscience, Vol. 15, No. 1 I, 01.01.1995, p. 419-428.

Research output: Contribution to journalArticle

Guenard, V. ; Gwynn, Lisa A ; Wood, Patrick. / Transforming growth factor-β blocks myelination but not ensheathment of axons by Schwann cells in vitro. In: Journal of Neuroscience. 1995 ; Vol. 15, No. 1 I. pp. 419-428.
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