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Science 21 March 2003:
Vol. 299. no. 5614, pp. 1889 - 1892
DOI: 10.1126/science.1079641
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Reports

Role of EphA4 and EphrinB3 in Local Neuronal Circuits That Control Walking

Klas Kullander,12* Simon J. B. Butt,3 James M. Lebret,3 Line Lundfald,3 Carlos E. Restrepo,3 Anna Rydström,2 Rüdiger Klein,4dagger Ole Kiehn3*dagger

Local circuits in the spinal cord that generate locomotion are termed central pattern generators (CPGs). These provide coordinated bilateral control over the normal limb alternation that underlies walking. The molecules that organize the mammalian CPG are unknown. Isolated spinal cords from mice lacking either the EphA4 receptor or its ligand ephrinB3 have lost left-right limb alternation and instead exhibit synchrony. We identified EphA4-positive neurons as an excitatory component of the locomotor CPG. Our study shows that dramatic locomotor changes can occur as a consequence of local genetic rewiring and identifies genes required for the development of normal locomotor behavior.

1 Department of Medical Biochemistry, Gothenburg University, Medicinaregatan 9 A, 405 30 Gothenburg, Sweden.
2 AstraZeneca Transgenics and Comparative Genomics, AstraZeneca, 431 83 Mölndal, Sweden.
3 Mammalian Locomotor Laboratory, Department of Neuroscience, The Karolinska Institute, Retzius vag 8, 171 77 Stockholm, Sweden.
4 Max-Planck Institute of Neurobiology, Am Klopferspitz 18A, D-82152 Martinsried, Germany.
*   To whom correspondence should be addressed. E-mail: klas.kullander{at}medkem.gu.se (K.K.); ole.kiehn{at}neuro.ki.se (O.K.)

dagger    These authors contributed equally to this work.

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