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Originally published In Press as doi:10.1074/jbc.M507130200 on December 22, 2005
J. Biol. Chem., Vol. 281, Issue 9, 5982-5991, March 3, 2006
Identification and Functions of Chondroitin Sulfate in the Milieu of Neural Stem Cells*
Michiru Ida ,
Takuya Shuo ¶,
Kanako Hirano ,
Yoshihito Tokita ,
Keiko Nakanishi ,
Fumiko Matsui ,
Sachiko Aono ,
Hiroshi Fujita||,
Yasuyuki Fujiwara¶,
Toshiyuki Kaji¶, and
Atsuhiko Oohira 1
From the
Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi 480-0392, Japan, the Department of Neurochemistry, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan, the ¶Department of Environmental Health, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa 920-1181, Japan, and ||Seikagaku Corporation, Yokosuka, Kanagawa 239-0831, Japan
The behavior of cells is generally considered to be regulated by environmental factors, but the molecules in the milieu of neural stem cells have been little studied. We found by immunohistochemistry that chondroitin sulfate (CS) existed in the surroundings of nestin-positive cells or neural stem/progenitor cells in the rat ventricular zone of the telencephalon at embryonic day 14. Brain-specific chondroitin sulfate proteoglycans (CSPGs), including neurocan, phosphacan/receptor-type protein-tyrosine phosphatase , and neuroglycan C, were detected in the ventricular zone. Neurospheres formed by cells from the fetal telencephalon also expressed these CSPGs and NG2 proteoglycan. To examine the structural features and functions of CS polysaccharides in the milieu of neural stem cells, we isolated and purified CS from embryonic day 14 telencephalons. The CS preparation consisted of two fractions differing in size and extent of sulfation: small CS polysaccharides with low sulfation and large CS polysaccharides with high sulfation. Interestingly, both CS polysaccharides and commercial preparations of dermatan sulfate CS-B and an E-type of highly sulfated CS promoted the fibroblast growth factor-2-mediated proliferation of neural stem/progenitor cells. None of these CS preparations promoted the epidermal growth factor-mediated neural stem cell proliferation. These results suggest that these CSPGs are involved in the proliferation of neural stem cells as a group of cell microenvironmental factors.
Received for publication, June 30, 2005
, and in revised form, December 13, 2005.
* This work was supported in part by grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and from the Japan Society for the Promotion of Science. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 To whom correspondence should be addressed: Dept. of Perinatology and Neuroglycoscience, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi 480-0392, Japan. Tel.: 81-568-88-0811; Fax: 81-568-88-0829; E-mail: oohira{at}inst-hsc.jp.

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Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.
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