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Vol. 15, Issue 5, 2093-2104, May 2004

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Versican V1 Isoform Induces Neuronal Differentiation and Promotes Neurite Outgrowth

Yaojiong Wu ^* , Wang Sheng ^* , Liwen Chen ^* , Haiheng Dong ^* , Vivian Lee ^* , Fred Lu ^* , C. Shun Wong ^* , Wei-Yang Lu ^* , and Burton B. Yang ^*  ||

^* Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada; Departments of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario Canada; Anaesthesia, University of Toronto, Toronto, Ontario Canada; and Radiation Oncology, University of Toronto, Toronto, Ontario Canada

Submitted September 15, 2003; Revised January 12, 2004; Accepted January 27, 2004
Monitoring Editor: Richard Hynes

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, whereas 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 epidermal growth factor receptor and integrins, and facilitated sustained extracellular signal-regulated kinase/MAPK phosphorylation. Blockade of the epidermal growth factor 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.

Abbreviations used: CNS, central nerve system; ECM, extracellular matrix; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; Erk, extracellular regulated kinase; FBS, fetal bovine serum; NGF, nerve growth factor.

^|| Corresponding author. E-mail address: burton.yang{at}sw.ca.

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