TY - JOUR T1 - Syndecan functions to regulate Wnt-dependent axon guidance in <em>C. elegans</em> JF - bioRxiv DO - 10.1101/046094 SP - 046094 AU - Samantha N. Hartin AU - Brian D. Ackley Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/03/28/046094.abstract N2 - Syndecans are conserved cell-surface receptors that function in multiple developmental contexts. We found that C. elegans with mutations in the single syndecan gene, sdn-1, exhibited errors in anterior-posterior axon growth and termination, including axons that stopped short of or grew past their stereotypical termination point. Transgenic rescue experiments indicated that syndecan function was cell non-autonomous for GABAergic axon outgrowth during early development, but likely cell autonomous to inhibit growth later in development. In regulating the posterior termination of the GABAergic motorneurons in the dorsal nerve cord, sdn-1 appeared to function to regulate the inhibitory activity of the egl-20/Wnt ligand. Over-expression of EGL-20 induced premature axon termination, and this was enhanced by loss of sdn-1. Conversely, removing egl-20 from sdn-1 mutants resulted in fewer animals with prematurely terminating dorsal nerve cords. The proteoglycan modifying enzymes hse-5 and hst-2, but not hst-6, had similar effects, suggesting specific heparan sulfate modifications regulated EGL-20 axon-terminating activity. sdn-1 appears to function with lin-17/Frizzled, bar-1/β-catenin and the egl-5 Hox-like transcription factor in EGL-20-depedent axon outgrowth. We found that bar-1 was required for egl-5 expression in the most posterior GABAergic neurons. sdn-1 mutants had a more variable effect on egl-5 expression, but over-expression of egl-5 was able to partially rescue phenotypes caused by the loss of sdn-1. Overall our results suggest that syndecan is a component of a specific Wnt-signaling event that is necessary for axons to recognize appropriate termination points. ER -