During nervous system development axons navigate through the extracellular matrix (ECM) to their target. Axons obtain the information where to grow from guidance cues located in the ECM or on cells neighbouring the growth path of the axon. A number of these guidance cues have been characterized in the past. However, there is increasing evidence that there are other molecules around that fine-tune the response of the axon to the various cues it senses. Heparan sulfate proteoglycans (HSPGs) are proteins that carry long sugar side chains. HSPGs have been shown to interact with a wide variety of morphogenes in vertebrates and invertebrates. We have previously described the role played by the HSPG Syndecan (SDN-1) during nervous system development in C. elegans. It is, however, still unknown through what mechanism SDN-1 exerts its function. Furthermore there is genetic evidence that there is at least one other HSPG core protein acting in parallel to SDN-1. With the aim to find genetic interactors of SDN-1, we performed forward genetic screens. We have screened about 20''000 genomes and isolated 10 candidate mutations. FLP and SNP mapping revealed that they map to 8 different intervals. Candidate
op481 is mapping to the middle of chromosome three to an interval not containing any previously described axon guidance gene. Sequencing revealed that
op481 carries a premature stop codon in the gene
zfp-1. We will show a first characterization of the function of
zfp-1 in axon guidance. Additionally epistasis analysis of the different candidates will show whether we identified multiple parallel signalling pathways.