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The Journal of Neuroscience, February 4, 2004, 24(5):1070-1078; doi:10.1523/JNEUROSCI.4719-03.2004

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Development/Plasticity/Repair
Ephrin-A5 Exerts Positive or Inhibitory Effects on Distinct Subsets of EphA4-Positive Motor Neurons

Johann Eberhart,¹ Jason Barr,¹ Sinead O'Connell,¹ Alleda Flagg,¹ Mary E. Swartz,¹ Karina S. Cramer,² Kathryn W. Tosney,³ Elena B. Pasquale,⁴ and Catherine E. Krull¹

¹Division of Biological Sciences, University of Missouri-Columbia, Columbia, Missouri 65211, ²Department of Neurobiology and Behavior, University of California-Irvine, Irvine, California 92697, ³Departments of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, and ⁴The Burnham Institute, La Jolla, California 92037

Eph receptor tyrosine kinases and ephrins are required for axon patterning and plasticity in the developing nervous system. Typically, Eph–ephrin interactions promote inhibitory events; for example, prohibiting the entry of neural cells into certain embryonic territories. Here, we show that distinct subsets of motor neurons that express EphA4 respond differently to ephrin-A5. EphA4-positive LMC(l) axons avoid entering ephrin-A5-positive hindlimb mesoderm. In contrast, EphA4-positive MMC(m) axons extend through ephrin-A5-positive rostral half-sclerotome. Blocking EphA4 activation in MMC(m) neurons or expanding the domain of ephrin-A5 expression in the somite results in the aberrant growth of MMC(m) axons into the caudal half-sclerotome. Moreover, premature expression of EphA4 in MMC(m) neurons leads to a portion of their axons growing into novel ephrin-A5-positive territories. Together, these results indicate that EphA4-ephrin-A5 signaling acts in a positive manner to constrain MMC(m) axons to the rostral half-sclerotome. Furthermore, we show that Eph activation localizes to distinct subcellular compartments of LMC(l) and MMC(m) neurons, consistent with distinct EphA4 signaling cascades in these neuronal subpopulations.

Key words: motor axon; Eph; ephrin; mesoderm; electroporation; chick

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Received Oct 19, 2003; revised December 8, 2003; accepted December 10, 2003.

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