Segregation of axial motor and sensory pathways via heterotypic trans-axonal signaling.
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.
Gallarda
Benjamin W
BW
Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Bonanomi
Dario
D
Müller
Daniel
D
Brown
Arthur
A
Alaynick
William A
WA
Andrews
Shane E
SE
Lemke
Greg
G
Pfaff
Samuel L
SL
Marquardt
Till
T
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
D036342:Ephrins; D008024:Ligands; C491717:Epha3 protein, mouse; D036121:Receptor, EphA3; D036122:Receptor, EphA4