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J. Biol. Chem., Vol. 281, Issue 17, 12123-12131, April 28, 2006

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Versican V0 and V1 Guide Migratory Neural Crest Cells^*

Shilpee Dutt¹, Maurice Kléber², Mattia Matasci, Lukas Sommer, and Dieter R. Zimmermann³

From the Laboratory of Molecular Biology, Department of Pathology, University Hospital Zurich, CH-8091 Zurich, Switzerland and the Department of Biology, Institute of Cell Biology, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland

We previously showed the selective expression of the chondroitin sulfate proteoglycans versican V0 and V1 in barrier tissues that impede the migration of neural crest cells during embryonic trunk development (Landolt, R. M., Vaughan, L., Winterhalter, K. H., and Zimmermann, D. R. (1995) Development 212, 2303-2312). To test for an active involvement of these isoforms in the guidance process, we have now established protocols to isolate intact versican V0 and V1 in quantities sufficient for functional experiments. Using stripe choice assays, we demonstrate that pure preparations of either a mixture of versican V0/V1 or V1 alone strongly inhibit the migration of multipotent Sox10/p75NTR double-positive early neural crest stem cells on fibronectin by interfering with cell-substrate adhesion. We show that this inhibition is largely core glycoprotein-dependent, as the complete removal of the glycosaminoglycan chains has only a minor effect on the inhibitory capacity. Our findings support the notion that versican variants V0 and V1 act, possibly in concert with other inhibitory molecules such as aggrecan and ephrins, in directing the migratory streams of neural crest cells to their appropriate target tissues.

Received for publication, October 4, 2005 , and in revised form, February 14, 2006.

^* This work was supported in part by grants from the Swiss National Science Foundation, the Hartmann Müller, the Lydia Hochstrasser, and the Velux Foundation (to D. R. Z.), and grants from the Swiss National Science Foundation and the National Center of Competence in Research "Neural Plasticity and Repair" (to L. S.). 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 Present address: Dept. of Laboratory Medicine, Children's Hospital, Harvard Medical School, Boston, MA 02115.

² Present e-mail address: maurice.kleber{at}gmx.ch.

³ To whom correspondence should be addressed. Tel.: 41-44-255-3945; Fax: 41-44-255-4440; E-mail: dieterzi{at}pathol.unizh.ch.

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