title: FGF-dependent generation of oligodendrocytes by a hedgehog-independent pathway.
abstract: During development, spinal cord oligodendrocyte precursors (OPCs) originate from the ventral, but not dorsal, neuroepithelium. Sonic hedgehog (SHH) has crucial effects on oligodendrocyte production in the ventral region of the spinal cord; however, less is known regarding SHH signalling and oligodendrocyte generation from neural stem cells (NSCs). We show that NSCs isolated from the dorsal spinal cord can generate oligodendrocytes following FGF2 treatment, a MAP kinase dependent phenomenon that is associated with induction of the obligate oligogenic gene Olig2. Cyclopamine, a potent inhibitor of hedgehog signalling, did not block the formation of oligodendrocytes from FGF2-treated neurosphere cultures. Furthermore, neurospheres generated from SHH null mice also produced oligodendrocytes, even in the presence of cyclopamine. These findings are compatible with the idea of a hedgehog independent pathway for oligodendrocyte generation from neural stem cells.
authors.affiliation: Cambridge Centre for Brain Repair, University of Cambridge, ED Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK. sc222@cam.ac.uk
authors.forename: Siddharthan
authors.initials: S
authors.lastname: Chandran
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Kato
authors.forename: Dianne
authors.initials: D
authors.lastname: Gerreli
authors.forename: Alastair
authors.initials: A
authors.lastname: Compston
authors.forename: Clive N
authors.initials: CN
authors.lastname: Svendsen
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Allen
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D053823:Hedgehog Proteins; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014704:Veratrum Alkaloids / Q000494:pharmacology
chemical_list: D017931:DNA Primers; D053823:Hedgehog Proteins; C465570:Shh protein, mouse; D015534:Trans-Activators; D014704:Veratrum Alkaloids; D016222:Fibroblast Growth Factor 2; C000541:cyclopamine