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Eph tyrosine kinase receptor EphA4 is required for the topographic mapping of the corticospical tract


Canty, A and Greferath, U and Turnley, AM and Murphy, M, Eph tyrosine kinase receptor EphA4 is required for the topographic mapping of the corticospical tract, National Academy of Sciences of The United States of America. Proceedings, 103, (42) pp. 15629-15634. ISSN 0027-8424 (2006) [Refereed Article]

Copyright Statement

Copyright 2006 by the National Academy of Sciences

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DOI: doi:10.1073/pnas.0607350103


Fine movement in the body is controlled by the motor cortex, which signals in a topographically specific manner to neurons in the spinal cord by means of the corticospinal tract (CST). How the correct topography of the CST is established is unknown. To investigate the possibility that the Eph tyrosine kinase receptor EphA4 is involved in this process, we have traced CST axons in mice in which the EphA4 gene has been deleted. The forelimb subpopulation of CST axons is unaffected in the EphA4-/- mice, but the hindlimb subpopulation branches too early within the cord, both temporally and spatially. EphA4 shows a dynamic expression pattern in the environment of the developing CST in the spinal cord: high at the time of forelimb branching and down-regulated before hindlimb branching. To examine whether the fore- and hindlimb subpopulations of CST axons respond differently to EphA4 in their environment, neurons from fore- and hindlimb motor cortex were cultured on a substrate containing EphA4. Neurons from the hindlimb cortex showed reduced branching on the EphA4 substrate compared with their forelimb counterparts. Neurons from the hindlimb cortex express ephrinA5, a high-affinity ligand for EphA4, at higher levels compared with forelimb cortex neurons, and this expression is down-regulated before hindlimb branching. Together, these findings suggest that EphA4 regulates topographic mapping of the CST by controlling the branching of CST axons in the spinal cord.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Canty, A (Associate Professor Alison Canty)
ID Code:69931
Year Published:2006
Web of Science® Times Cited:20
Deposited By:Medicine
Deposited On:2011-05-25
Last Modified:2011-05-26

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