Growth factor control of CNS myelination.
The molecular signals required for initiating myelination and maintenance of the myelin internode are not known. Several growth factor families have been implicated in promoting oligodendrocyte survival or differentiation and may have consequences on formation of myelin. We developed a reliable assay for detecting ensheathment of neurites by oligodendrocytes in spinal cord explants. This system was used to assay the effect of selected growth factors on myelin internode formation. We examined the influence on myelination of the polypeptide growth factors neuregulin (NRG), platelet-derived growth factor (PDGF), leukemia inhibitory factor (LIF), and the thyroid hormone T(3). We found that NRG, PDGF, and T(3) treatments enhanced myelination while LIF treatment inhibited it. We furthermore found that the most potent combination of factors to enhance myelination was NRG and T(3). Our results demonstrate that the role of growth factors on CNS myelination can be reliably studied in a controlled in vitro environment and that the impact of individual or combinations of growth factors on myelination cannot be predicted by their known effects on oligodendrocyte survival, proliferation, or differentiation.
Park
S K
SK
Department of Neurology, Beth Israel Deaconess Medical Center, Program in Neuroscience, Harvard Medical School, Boston, MA, USA.
Solomon
D
D
Vartanian
T
T
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D005333:Fetus; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006133:Growth Substances / Q000378:metabolism*; D007150:Immunohistochemistry; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D020880:Neuregulins / Q000378:metabolism / Q000494:pharmacology; D016900:Neurofilament Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology; D009418:S100 Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism / Q000494:pharmacology
D000943:Antigens, Differentiation; D006131:Growth Inhibitors; D006133:Growth Substances; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D004676:Myelin Basic Protein; D020880:Neuregulins; D016900:Neurofilament Proteins; D010982:Platelet-Derived Growth Factor; D009418:S100 Proteins; C036505:oligodendrocyte O antigen, mouse; C075278:platelet-derived growth factor A; D014284:Triiodothyronine