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First published online December 1, 2003
doi: 10.1242/10.1242/dev.00871

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FGF-dependent generation of oligodendrocytes by a hedgehog-independent pathway

Siddharthan Chandran^1,*, Hidemasa Kato², Dianne Gerreli³, Alastair Compston¹, Clive N. Svendsen⁴ and Nicholas D. Allen^2,

¹ Cambridge Centre for Brain Repair, University of Cambridge, ED Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK
² The Babraham Institute, Babraham, Cambridge CB2 4AT, UK
³ Neural Development Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK
⁴ Waisman Center Stem Cell Research Program, University of Wisconsin-Madison, 1500 Highland Avenue, Madison, WI 53705, USA

^* Author for correspondence (e mail: sc222{at}cam.ac.uk)

Accepted 16 September 2003

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.

Key words: Stem cell, Oligodendrocyte, FGF2, Spinal cord, Sonic hedgehog, OLIG2, NKX2.2

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