title: Segregation of axial motor and sensory pathways via heterotypic trans-axonal signaling.
abstract: Execution of motor behaviors relies on circuitries effectively integrating immediate sensory feedback to efferent pathways controlling muscle activity. It remains unclear how, during neuromuscular circuit assembly, sensory and motor projections become incorporated into tightly coordinated, yet functionally separate pathways. We report that, within axial nerves, establishment of discrete afferent and efferent pathways depends on coordinate signaling between coextending sensory and motor projections. These heterotypic axon-axon interactions require motor axonal EphA3/EphA4 receptor tyrosine kinases activated by cognate sensory axonal ephrin-A ligands. Genetic elimination of trans-axonal ephrin-A --> EphA signaling in mice triggers drastic motor-sensory miswiring, culminating in functional efferents within proximal afferent pathways. Effective assembly of a key circuit underlying motor behaviors thus critically depends on trans-axonal signaling interactions resolving motor and sensory projections into discrete pathways.
authors.affiliation: Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Gallarda
authors.forename: Dario
authors.initials: D
authors.lastname: Bonanomi
authors.forename: Daniel
authors.initials: D
authors.lastname: Müller
authors.forename: Arthur
authors.initials: A
authors.lastname: Brown
authors.forename: William A
authors.initials: WA
authors.lastname: Alaynick
authors.forename: Shane E
authors.initials: SE
authors.lastname: Andrews
authors.forename: Greg
authors.initials: G
authors.lastname: Lemke
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Pfaff
authors.forename: Till
authors.initials: T
authors.lastname: Marquardt
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004525:Efferent Pathways / Q000502:physiology; D004594:Electrophysiology; D036342:Ephrins / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D020439:Growth Cones / Q000502:physiology; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D009046:Motor Neurons / Q000502:physiology*; D018482:Muscle, Skeletal / Q000294:innervation; D009154:Mutation; D009475:Neurons, Afferent / Q000502:physiology*; D010525:Peripheral Nerves / Q000166:cytology / Q000502:physiology; D036121:Receptor, EphA3 / Q000235:genetics / Q000378:metabolism*; D036122:Receptor, EphA4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D036342:Ephrins; D008024:Ligands; C491717:Epha3 protein, mouse; D036121:Receptor, EphA3; D036122:Receptor, EphA4