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The Stem Cell Niche
Version of Record online: 19 JAN 2010
Copyright © 2010 AlphaMed Press
Volume 28, Issue 4, pages 775–787, April 2010
How to Cite
Sirko, S., von Holst, A., Weber, A., Wizenmann, A., Theocharidis, U., Götz, M. and Faissner, A. (2010), Chondroitin Sulfates Are Required for Fibroblast Growth Factor-2-Dependent Proliferation and Maintenance in Neural Stem Cells and for Epidermal Growth Factor-Dependent Migration of Their Progeny. STEM CELLS, 28: 775–787. doi: 10.1002/stem.309
Author contributions: S.S., A.v.H.: Conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing; A. Weber, A. Wizenmann: Collection of data; U.T.: Collection and assembly of data; M.G.: Conception and design, financial support, administrative support; data analysis and interpretation, manuscript writing, final approval of the manuscript; A.F.: Conception and design, financial support, administrative support; manuscript writing, data interpretation, final approval of the manuscript.
First published online in STEM CELLS EXPRESS December 23, 2009.
Disclosure of potential conflicts of interest is found at the end of this article.
- Issue online: 14 APR 2010
- Version of Record online: 19 JAN 2010
- Manuscript Accepted: 23 DEC 2009
- Manuscript Received: 22 JUL 2009
- Federal Ministry of Research and Technology
- Stem Cells for Therapies of the Central Nervous System. Grant Number: 01GN0504
- German Research Council
- Ministerium für Innovation, Wissenschaft, Forschung und Technologie (MIWFT) of Nordrhein-Westfalen (NRW)
- DFG, European union (EU)
- Bavarian Ministry of Science and Arts
- Extracellular matrix;
The neural stem cell niche of the embryonic and adult forebrain is rich in chondroitin sulfate glycosaminoglycans (CS-GAGs) that represent complex linear carbohydrate structures on the cell surface of neural stem/progenitor cells or in their intimate environment. We reported earlier that the removal of CS-GAGs with the bacterial enzyme chondroitinase ABC (ChABC) reduced neural stem/progenitor cell proliferation and self-renewal, whereas this treatment favored astroglia formation at the expense of neurogenesis. Here, we studied the consequences of CS-deglycanation further and revealed that CS-GAGs are selectively required for neurosphere formation, proliferation, and self-renewal of embryonic cortical neural stem/progenitor cells in response to fibroblast growth factor (FGF)-2. Consistently, the FGF-2-dependent activation of the MAPKinase in neural stem/progenitor cells was diminished after ChABC treatment, but unaltered after epidermal growth factor (EGF) stimulation. Upon EGF treatment, fewer radial glia were brain lipid-binding protein (BLBP)-positive, whereas more were glutamate aspartate transporter (GLAST)-positive after CS-GAG removal. Only in this latter situation, GLAST-positive radial glia cells extended processes that supported neuronal migration from differentiating neurospheres. CS-deglycanation also selectively increased astrocyte numbers and their migration in response to EGF. Thus, our approach revealed that CS-GAGs are essential for FGF-2-mediated proliferation and maintenance of neuron-generating neural stem/progenitor cells. Simultaneously, CS-GAGs act as a brake on the EGF-dependent maturation, migration, and gliogenesis of neural stem/progenitor cells. We conclude that neural stem/progenitor cell subpopulations reside in neurospheres that are distinguishable by their responsiveness to FGF-2 and EGF which is differentially regulated by CS-carbohydrate structures. STEM CELLS 2010;28:775–787