Elucidating The SAX-3/Roundabout-mediated Axon Outgrowth Termination Pathway in C. elegans

During development, neurons extend their axons to target regions and terminate axon outgrowth once that region is reached. In humans, after development, most neurons in the peripheral nervous system (PNS) continue to have axon outgrowth capabilities, while neurons in the central nervous system (CNS) do not. We are interested in utilizing the genetic model organism Caenorhabditis elegans to study the molecular mechanisms that underlie axon outgrowth termination. Previously, our lab determined that the secreted ligand SLT-1/Slit and the IgSF transmembrane receptor SAX-3/Roundabout, previously known to act together to direct ventral axon guidance during development, mediate axon outgrowth termination in the PHB sensory neurons of C. elegans. In addition, we have determined that several other molecules including UNC-33, UNC-34, UNC-69, and UNC-73 promote PHB axon outgrowth. Our goal is to elucidate the SAX-3-mediated axon outgrowth termination pathway. We hypothesize that a subset of these molecules will function in this pathway, downstream of SAX-3. To determine if these genes act downstream of sax-3, we will perform epistasis analysis.  Specifically, we will generate double mutant with sax-3 and each of the other candidate pathway members. Our preliminary results suggest that unc-33 is epistatic to sax-3 and therefore likely functions downstream of sax-3 in this pathway.