During development of the nervous system, growing axons rely on guidance molecules to direct axon pathfinding. A well-characterized family of guidance molecules are 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. We also show that EFN-4 probably functions as a diffusible factor because 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.
Bibliographical noteFunding Information:
This work is supported in part by Kennesaw State University?s Center for Excellence in Teaching and Learning and the Office of the Vice President for Research to M.L.H. and by the National Institutes of Health [R15 GM080701 to J.M. and RO1 NS045873 to L.C.]. Deposited in PMC for release after 12 months.
© 2016, Published by The Company of Biologists Ltd.
- Axon guidance
- C. elegans