RT Journal Article
SR Electronic
T1 Genetic Evidence for a Contribution of EphA:EphrinA Reverse Signaling to Motor Axon Guidance
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5209
OP 5215
DO 10.1523/JNEUROSCI.5707-11.2012
VO 32
IS 15
A1 Dudanova, Irina
A1 Kao, Tzu-Jen
A1 Herrmann, Julia E.
A1 Zheng, Binhai
A1 Kania, Artur
A1 Klein, Rüdiger
YR 2012
UL http://www.jneurosci.org/content/32/15/5209.abstract
AB Repulsive Eph forward signaling from limb-derived ephrins guides the axons of lateral motor column (LMC) motor neurons. LMC axons also express ephrinAs, while their EphA receptors are expressed in the limb mesenchyme. In vitro studies have suggested that reverse signaling from limb-derived EphA4 to axonal ephrinAs might result in attraction of LMC axons. However, genetic evidence for this function is lacking. Here we use the Dunn chamber turning assay to show that EphA proteins are chemoattractants and elicit fast turning responses in LMC neurons in vitro. Moreover, ectopic expression of EphA4 in chick hindlimb changes the limb trajectory of LMC axons. Nervous system-specific deletion of EphA4 in mice resulted in fewer LMC axon projection errors than the ubiquitous deletion of EphA4. Additionally, a signaling-incompetent EphA4 mutant partially rescued guidance errors in the hindlimb, suggesting that limb-derived EphA4 contributes to the establishment of LMC projections. In summary, we provide evidence for a role of EphA:ephrinA attractive reverse signaling in motor axon guidance and in vivo evidence of in-parallel forward Eph and reverse ephrin signaling function in the same neuronal population.