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Science 11 April 2008:
Vol. 320. no. 5873, pp. 233 - 236
DOI: 10.1126/science.1153758
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Reports

Segregation of Axial Motor and Sensory Pathways via Heterotypic Trans-Axonal Signaling

Benjamin W. Gallarda,1* Dario Bonanomi,1* Daniel Müller,2,3* Arthur Brown,4 William A. Alaynick,1 Shane E. Andrews,1 Greg Lemke,5 Samuel L. Pfaff,1{dagger} Till Marquardt2,3{dagger}

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.

1 Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
2 Developmental Neurobiology Laboratory, European Neuroscience Institute Göttingen, Max Planck Society/University Medical School Göttingen, Grisebachstrasse 5, 37077 Göttingen, Germany.
3 Deutsche Forschungsgemeinschaft Emmy Noether Group, European Neuroscience Institute Göttingen, Grisebach-strasse 5, 37077 Göttingen, Germany.
4 Biotherapeutics Research Group, Robarts Research Institute, Department of Anatomy and Cell Biology, University of Western Ontario, 100 Perth Drive, London, Ontario N6A 5K8, Canada.
5 Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: till.marquardt{at}mpi-mail.mpg.de (T.M.); pfaff{at}salk.edu (S.L.P.)

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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S. E. Baranzini, N. W. Galwey, J. Wang, P. Khankhanian, R. Lindberg, D. Pelletier, W. Wu, B. M.J. Uitdehaag, L. Kappos, GeneMSA Consortium, et al. (2009)
Hum. Mol. Genet. 18, 2078-2090
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Crystal Structure and NMR Binding Reveal That Two Small Molecule Antagonists Target the High Affinity Ephrin-binding Channel of the EphA4 Receptor.
H. Qin, J. Shi, R. Noberini, E. B. Pasquale, and J. Song (2008)
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Science. ISSN 0036-8075 (print), 1095-9203 (online)