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The Journal of Neuroscience, April 12, 2006, 26(15):4082-4094; doi:10.1523/JNEUROSCI.0422-06.2006

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Development/Plasticity/Repair
The Unique 473HD-Chondroitinsulfate Epitope Is Expressed by Radial Glia and Involved in Neural Precursor Cell Proliferation

Alexander von Holst, ^* Swetlana Sirko, ^* and Andreas Faissner

Chair Cell Morphology and Molecular Neurobiology, Faculty of Biology, Ruhr-University Bochum, D-44780 Bochum, Germany

Correspondence should be addressed to Prof. Andreas Faissner, Chair Cell Morphology and Molecular Neurobiology, Faculty of Biology, Ruhr-University Bochum, NDEF 05/594, Universitätsstrasse 150, D-44780 Bochum, Germany. Email: andreas.faissner{at}ruhr-uni-bochum.de

Neural stem cells have been documented in both the developing and the mature adult CNSs of mammals. This cell population holds a considerable promise for therapeutical applications in a wide array of CNS diseases. Therefore, universally applicable strategies for the purification of this population to further its cell biological characterization are sought. Here, we report that the unique chondroitin sulfate epitope recognized by the monoclonal antibody 473HD is surface expressed on actively cycling, multipotent progenitor cells of the developing telencephalon with radial glia-like properties. When used for immunopanning, the antibody enriched at least threefold for neural stem/progenitor cells characterized by the ability to self-renew as neurospheres that generated all major neural lineages in differentiation assays. In contrast, the 473HD-depleted cell fraction was mostly devoid of neurosphere-forming cells. The isolation of 473HD-positive adult multipotent progenitors from the subependymal zone of the lateral ventricle wall revealed a substantial overlap with the known adult neural stem cell marker LewisX. When the chondroitin sulfates were removed from immunoselected 473HD-positive neural stem/progenitor cell surfaces by chondroitinase ABC treatment or perturbed by the monoclonal antibody 473HD that recognizes the unique DSD-1 chondroitin sulfate epitope, the generation of neurospheres was significantly reduced. Thus, the 473HD epitope could not only be used for the isolation of multipotent neural progenitors during forebrain development as well as from the adult neurogenic niche but may also constitute a functionally important entity of the neural stem cell niche.

Key words: monoclonal antibody; extracellular matrix; marker; neural precursor; neurogenesis; cell fate; gliogenesis; stem cells; subventricular zone

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Received Oct. 7, 2005; revised March 3, 2006; accepted March 7, 2006.

Correspondence should be addressed to Prof. Andreas Faissner, Chair Cell Morphology and Molecular Neurobiology, Faculty of Biology, Ruhr-University Bochum, NDEF 05/594, Universitätsstrasse 150, D-44780 Bochum, Germany. Email: andreas.faissner{at}ruhr-uni-bochum.de

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