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 language | English |
|---|---|
| Pages (from-to) | 419-428 |
| Number of pages | 10 |
| Journal | Journal of Neuroscience |
| Volume | 15 |
| Issue number | 1 I |
| State | Published - Jan 1 1995 |
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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 journal › Article
}
TY - JOUR
T1 - Transforming growth factor-β blocks myelination but not ensheathment of axons by Schwann cells in vitro
AU - Guenard, V.
AU - Gwynn, Lisa A
AU - Wood, Patrick
PY - 1995/1/1
Y1 - 1995/1/1
N2 - 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.
AB - 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.
KW - differentiation
KW - myelination
KW - neuron
KW - Schwann cell
KW - transforming growth factor-β
UR - http://www.scopus.com/inward/record.url?scp=0029137658&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029137658&partnerID=8YFLogxK
M3 - Article
C2 - 7823146
AN - SCOPUS:0029137658
VL - 15
SP - 419
EP - 428
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 1 I
ER -