| Abstract No.: | C-A3006 |
| Country: | Canada |
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| Title: | ROLE OF HEPARAN SULPHATE PROTEOGLYCANS IN NETRIN-MEDIATED AXON GROWTH |
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| Authors/Affiliations: | 1 K. Adam Baker*; 1 Simon Moore; 1 Sonia Rodrigues; 1 Timothy Kennedy;
1 Montreal Neurological Institute, QC, Canada
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| Content: | Objectives: Heparan sulphate proteoglycans (HSPGs) are a complex family of extracellular matrix molecules that play important roles in nervous system development. Netrin-1 is a secreted chemotropic guidance cue that is essential for appropriate commissural axon extension during neural development. Netrin-1 binds heparin with high affinity. Here we investigate the functional significance of this interaction.
Material and Methods: Embryonic rat dorsal spinal commissural explants were cultured in a three dimensional collagen matrix. Using this assay, we investigated the influence of heparanase and heparin on commissural axon outgrowth in response to netrin-1.
Results: Treatment of dorsal spinal cord explants with heparanase significantly reduced netrin-induced commissural axon outgrowth. Furthermore, co-treatment of explants with heparin and sub-optimal concentrations of netrin-1 enhanced DCC-dependant outgrowth to levels seen with optimal concentrations of netrin-1 alone.
Conclusions: These results provide evidence that HSPGs are important for netrin-mediated axon outgrowth and that HSPGs and netrin-1 work synergistically to promote axon growth.
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