FGF-dependent generation of oligodendrocytes by a hedgehog-independent pathway
Author:
Chandran Siddharthan1, Kato Hidemasa2, Gerreli Dianne3, Compston Alastair1, Svendsen Clive N.4, Allen Nicholas D.2
Affiliation:
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
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.
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Reference73 articles.
1. Alberta, J. A., Park, S. K., Mora, J., Yuk, D., Pawlitzky, I.,Iannarelli, P., Vartanian, T., Stiles, C. D. and Rowitch, D. H.(2001). Sonic hedgehog is required during an early phase of oligodendrocyte development in mammalian brain. Mol. Cell Neurosci.18,434-441. 2. Barth, K. A., Kishimoto, Y., Rohr, K. B., Seydler, C.,Schulte-Merker, S. and Wilson, S. W. (1999). Bmp activity establishes a gradient of positional information throughout the entire neural plate. Development126,4977-4987. 3. Basler, K., Edlund, T., Jessell, T. M. and Yamada, T.(1993). Control of cell pattern in the neural tube: regulation of cell differentiation by dorsalin-1, a novel TGF beta family member. Cell73,687-702. 4. Boilly, B., Vercoutter-Edouart, A. S., Hondermarck, H.,Nurcombe, V. and Le Bourhis, X. (2000). FGF signals for cell proliferation and migration through different pathways. Cytokine Growth Factor Rev.11,295-302. 5. Briscoe, J., Sussel, L., Serup, P., Hartigan-O'Connor, D.,Jessell, T. M., Rubenstein, J. L. and Ericson, J. (1999). Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling. Nature398,622-627.
Cited by
112 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献
|
|