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Molecular and Cellular Biology, November 2003, p. 8092-8098, Vol. 23, No. 22
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.22.8092-8098.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

EphA3 Null Mutants Do Not Demonstrate Motor Axon Guidance Defects

Ashish Vaidya,1,2 Anna Pniak,1,2 Greg Lemke,3 and Arthur Brown1,2*

Stem Cell Biology and Regenerative Medicine and Biotherapeutics Research Groups, Robarts Research Institute,1 Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario N6A 5K8, Canada,2 Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California3

Received 18 November 2002/ Returned for modification 27 January 2003/ Accepted 24 February 2003

Motor axon projections are topographically ordered. Medial motor column axons project to axial muscles, whereas lateral motor column axons project to limb muscles and, along the rostrocaudal axis of the animal, the more rostral motor neuron pools project to more rostral muscle targets. We have shown that EphA3 is specifically expressed in the developing medial motor column and have postulated that EphA3 might be responsible for directing their axons to axial muscle targets. This hypothesis was supported by our demonstration that EphA3 can direct retinal ganglion cell axon targeting and by studies of ephrin-A5-/- mutants that show that EphA receptor signaling controls the topographic innervation of the acromiotrapezius. To test the role of EphA3 in motor axon guidance, we generated an EphA3 null mutant. Retrograde labeling studies in EphA3-/- embryos and adults indicate that, contrary to our predictions, EphA3 is not necessary to direct motor axons to axial muscle targets. Our results also demonstrate that ephrin A5's ability to direct topographic innervation of the acromiotrapezius must be mediated through EphA receptors other than, or in addition to, EphA3.

* Corresponding author. Mailing address: Biotherapeutics Research Group, The Robarts Research Institute, 100 Perth Dr., London, Ontario N6A 5K8, Canada. Phone: (519) 663-5777. Fax: (519) 663-3789. E-mail: abrown{at}robarts.ca.

Molecular and Cellular Biology, November 2003, p. 8092-8098, Vol. 23, No. 22
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.22.8092-8098.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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