title: Neural cell adhesion molecule stimulates survival of premyelinating oligodendrocytes via the fibroblast growth factor receptor.
abstract: Axonal signals are critical in promoting the survival and maturation of oligodendrocytes during myelination, with contact-dependent signals thought to play a key role. However, the exact nature of these signals remains unclear. Neural cell adhesion molecule (NCAM) is expressed by both axons and oligodendrocytes and is ideally localized to transduce signals from the axon. This study sought to investigate the influence of NCAM on premyelinating oligodendrocytes in vitro. Both a soluble molecule comprising the extracellular domain of NCAM and a peptide derived from the fibroblast growth factor receptor (FGFR) binding motif within the first fibronectin domain stimulated a dose-dependent increase in survival of premyelinating oligodendrocytes in vitro. The survival effect was blocked by a mitogen-activated protein kinase (MAPK) inhibitor and an FGFR inhibitor, suggesting that activation of MAPK signalling pathways following interaction with the FGFR is involved in the survival effect of NCAM. Furthermore, NCAM presented in a cellular monolayer induced an increase in radial process outgrowth of oligodendrocyte progenitor cells. These data suggest that NCAM may play a role in axon-oligodendrocyte signalling during myelination, leading to an increase in oligodendrocyte survival and process outgrowth following axonal contact.
authors.affiliation: Department of Cellular and Molecular Neuroscience, Wolfson Neuroscience Laboratories, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Palser
authors.forename: Adele L
authors.initials: AL
authors.lastname: Norman
authors.forename: Jane L
authors.initials: JL
authors.lastname: Saffell
authors.forename: Richard
authors.initials: R
authors.lastname: Reynolds
mesh_terms: D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D048430:Cell Shape / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism*; D041681:NIH 3T3 Cells; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects / Q000378:metabolism*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D019006:Neural Cell Adhesion Molecules; D010446:Peptide Fragments; D017468:Receptors, Fibroblast Growth Factor