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First published online 27 June 2007
doi: 10.1242/dev.02871

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Chondroitin sulfate glycosaminoglycans control proliferation, radial glia cell differentiation and neurogenesis in neural stem/progenitor cells

Swetlana Sirko^1,*, Alexander von Holst^1,*, Andrea Wizenmann², Magdalena Götz^2,3 and Andreas Faissner^1,

¹ Chair of Cell Morphology and Molecular Neurobiology, Ruhr-University Bochum, Building NDEF 05/339, Universitaetsstrasse 150, D-44780 Bochum, Germany.
² GSF-Institute for Stem Cell Research, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany.
³ Institute of Physiology, University of Munich, Schillerstaße 46, D-80634 München, Germany.

Author for correspondence (e-mail: andreas.faissner{at}ruhr-uni-bochum.de)

Accepted 24 May 2007

Although the local environment is known to regulate neural stem cell (NSC) maintenance in the central nervous system, little is known about the molecular identity of the signals involved. Chondroitin sulfate proteoglycans (CSPGs) are enriched in the growth environment of NSCs both during development and in the adult NSC niche. In order to gather insight into potential biological roles of CSPGs for NSCs, the enzyme chondroitinase ABC (ChABC) was used to selectively degrade the CSPG glycosaminoglycans. When NSCs from mouse E13 telencephalon were cultivated as neurospheres, treatment with ChABC resulted in diminished cell proliferation and impaired neuronal differentiation, with a converse increase in astrocytes. The intrauterine injection of ChABC into the telencephalic ventricle at midneurogenesis caused a reduction in cell proliferation in the ventricular zone and a diminution of self-renewing radial glia, as revealed by the neurosphere-formation assay, and a reduction in neurogenesis. These observations suggest that CSPGs regulate neural stem/progenitor cell proliferation and intervene in fate decisions between the neuronal and glial lineage.

Key words: Chondroitinase ABC, Astrocyte differentiation, Stem cell niche, Proteoglycans

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