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A more recent version of this article appeared on May 1, 2004
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Submitted on September 15, 2003
Revised on January 12, 2004
Accepted on January 27, 2004
1 Sunnybrook & Women’s College Health Sciences Centre; Department of Laboratory Medicine and Pathobiology, University of Toronto
2 Sunnybrook & Women’s College Health Sciences Centre; Department of Anaesthesia, University of Toronto
3 Sunnybrook & Women’s College Health Sciences Centre; Department of Radiation Oncology, University of Toronto
* Corresponding author. E-mail address: burton.yang{at}sw.ca.
The chondroitin sulfate proteoglycan versican is one of the major extracellular components in the developing and adult brain. Here we show that isoforms of versican play different roles in neuronal differentiation and neurite outgrowth. Expression of versican V1 isoform in PC12 cells induced complete differentiation, while expression of V2 induced an aborted differentiation accompanied by apoptosis. V1 promoted neurite outgrowth of hippocampal neurons but V2 failed to do so. V1 transfection enhanced expression of EGF receptor and integrins, and facilitated sustained ERK/MAPK phosphorylation. Blockade of the EGF receptor, 
1 integrin, or Src significantly inhibited neuronal differentiation. Finally, we demonstrated that versican V1 isoform also promoted differentiation of neural stem cells into neurons. Our results have implications for understanding how versican regulates neuronal development, function, and repair.
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