Syndecan functions to regulate Wnt-dependent axon guidance in C. elegans

Abstract

Cell adhesion molecules are key to axon guidance during development, for example specific cues can instruct axons to terminate in a specific area, or to continue growth. Syndecans are conserved cell-surface receptors that function in multiple developmental contexts. Caenorhabditis elegans with mutations in the single syndecan gene, sdn-1, exhibited errors in anterior-posterior guidance, with axons that stopped short of, or grew past their stereotypical termination point. Syndecan function was cell non-autonomous for GABAergic axon outgrowth during early development, but was likely cell autonomous to inhibit growth later in development. sdn-1 appeared to regulate the inhibitory activity of the egl-20/Wnt ligand. Removing egl-20 from sdn-1 mutants resulted in fewer animals with prematurely terminating axons. 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 functioned with lin-17/Frizzled, bar-1/{beta}-catenin and the egl-5 Hox-like transcription factor in EGL-20-depedent axon outgrowth. bar-1 was required for egl-5 expression in the most posterior GABAergic neurons. sdn-1 mutations did not eliminate egl-5 expression, but over-expression of egl-5 rescued sdn-1 phenotypes. Our results suggest syndecan is a component of Wnt-signaling events that are necessary for axons to recognize appropriate termination points.