EFN-4/Ephrin functions in LAD-2/L1CAM-mediated axon guidance in Caenorhabditis elegans

Abstract

During nervous system development, growing axons rely on guidance molecules to direct axon pathfinding. A well-characterized family of guidance molecules is the membrane-associated ephrins, which together with their cognate Eph receptors, direct axon navigation in a contact-mediated fashion. In C. elegans, the ephrin-Eph signaling system is conserved and is best characterized for their roles in neuroblast migration during early embryogenesis. This study demonstrates a role for the C. elegans ephrin, EFN-4 in axon guidance. We provide both genetic and biochemical evidence that is consistent with the C. elegans divergent L1 cell adhesion molecule, LAD-2, acting as a non-canonical ephrin receptor to EFN-4 to promote axon guidance. Lastly, we show that EFN-4 likely functions as a diffusible factor as EFN-4 engineered to be soluble can promote LAD-2-mediated axon guidance. This study thus reveals a potential additional mechanism for ephrins in regulating axon guidance and expands the repertoire of receptors by which ephrins can signal.