TY - JOUR
T1 - Contrasting effects of mitogenic growth factors on myelination in neuron-oligodendrocyte co-cultures
AU - Wang, Zhen
AU - Colognato, Holly
AU - Ffrench-Constant, Charles
PY - 2007/1/18
Y1 - 2007/1/18
N2 - Mitogenic growth factors play an important role in the initial stages of oligodendrocyte development, but their roles in the process of myelination itself remain less well defined. In order to study directly the effects of different growth factors on myelination, we used a purified in vitro co-culture system with dorsal root ganglion neurons and oligodendrocytes. Extensive myelination had occurred in these cultures 14 days after oligodendrocyte precursors (OPCs) were added, with the relationship between neurite density and the percentage of oligodendrocytes forming myelin sheaths providing a robust and straightforward means of quantifying myelination. Addition of soluble neuregulin (Nrg1), a mitogen for oligodendroglial cells that also provides an axonal signal implicated in oligodendrocyte survival, increased myelination. Conversely, the OPC mitogens FGF-2 and PDGF inhibited myelination. The inhibitory effect of these mitogens was reversible, as inhibition of PDGF allowed myelination to proceed. Taken together, these data indicate that different mitogenic growth factors can regulate myelination by oligodendrocytes in addition to their well-described effects on earlier stages of oligodendroglial development. Moreover, the results highlight important differences between the growth factors.
AB - Mitogenic growth factors play an important role in the initial stages of oligodendrocyte development, but their roles in the process of myelination itself remain less well defined. In order to study directly the effects of different growth factors on myelination, we used a purified in vitro co-culture system with dorsal root ganglion neurons and oligodendrocytes. Extensive myelination had occurred in these cultures 14 days after oligodendrocyte precursors (OPCs) were added, with the relationship between neurite density and the percentage of oligodendrocytes forming myelin sheaths providing a robust and straightforward means of quantifying myelination. Addition of soluble neuregulin (Nrg1), a mitogen for oligodendroglial cells that also provides an axonal signal implicated in oligodendrocyte survival, increased myelination. Conversely, the OPC mitogens FGF-2 and PDGF inhibited myelination. The inhibitory effect of these mitogens was reversible, as inhibition of PDGF allowed myelination to proceed. Taken together, these data indicate that different mitogenic growth factors can regulate myelination by oligodendrocytes in addition to their well-described effects on earlier stages of oligodendroglial development. Moreover, the results highlight important differences between the growth factors.
KW - ErbB4
KW - Fibroblast growth factor
KW - Myelin
KW - Nerve growth factor
KW - Neuregulin
KW - Platelet-derived growth factor
UR - http://www.scopus.com/inward/record.url?scp=33847700862&partnerID=8YFLogxK
U2 - 10.1002/glia.20480
DO - 10.1002/glia.20480
M3 - Article
C2 - 17236210
AN - SCOPUS:33847700862
VL - 55
SP - 537
EP - 545
JO - Glia
JF - Glia
SN - 0894-1491
IS - 5
ER -