PT  - JOURNAL ARTICLE
AU  - Alicia A. Schwieterman
AU  - Alyse N. Steves
AU  - Vivian Yee
AU  - Cory J. Donelson
AU  - Aaron Pital
AU  - Taylor Voyles
AU  - Austin M. Howard
AU  - Danielle E. Ereddia
AU  - Kelsie S. Effrein
AU  - Jonathan L. McMurry
AU  - Brian D. Ackley
AU  - Andrew D. Chisholm
AU  - Martin L. Hudson
TI  - The <em>C. elegans</em> ephrin EFN-4 functions non-cell autonomously with heparan sulfate proteoglycans to promote axon outgrowth and branching
AID  - 10.1101/022756
DP  - 2015 Jan 01
TA  - bioRxiv
PG  - 022756
4099  - http://biorxiv.org/content/early/2015/07/17/022756.short
4100  - http://biorxiv.org/content/early/2015/07/17/022756.full
AB  - The Eph receptors and their cognate ephrin ligands play key roles in many aspects of nervous system development. These interactions typically occur within an individual tissue type, serving either to guide axons to their terminal targets or to define boundaries between the rhombomeres of the hindbrain. We have identified a novel role for the Caenorhabditis elegans ephrin EFN-4 in promoting primary neurite outgrowth in AIY interneurons and D-class motor neurons. Rescue experiments reveal that EFN-4 functions non-cell autonomously in the epidermis to promote primary neurite outgrowth. We also find that EFN-4 plays a role in promoting ectopic axon branching in a C. elegans model of X-linked Kallmann syndrome. In this context, EFN-4 functions non-cell autonomously in the body wall muscle, and in parallel with HS biosynthesis genes and HSPG core proteins, which function cell autonomously in the AIY neurons. This is the first report of an epidermal ephrin providing a developmental cue to the nervous system.