Syndecan functions to regulate Wnt-dependent axon guidance inC. elegans

AbstractCell 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 eleganswith 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-1appeared to regulate the inhibitory activity of theegl-20/Wntligand. Removingegl-20fromsdn-1mutants resulted in fewer animals with prematurely terminating axons. The proteoglycan modifying enzymeshse-5andhst-2, but nothst-6, had similar effects, suggesting specific heparan sulfate modifications regulated EGL-20 axon-terminating activity.sdn-1functioned withlin-17/Frizzled,bar-1/β-catenin and theegl-5Hox-like transcription factor in EGL-20-depedent axon outgrowth.bar-1was required foregl-5expression in the most posterior GABAergic neurons.sdn-1mutations did not eliminateegl-5expression, but over-expression ofegl-5rescuedsdn-1phenotypes. Our results suggest syndecan is a component of Wnt-signaling events that are necessary for axons to recognize appropriate termination points.