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The Journal of Neuroscience, November 4, 2009, 29(44):13981-13991; doi:10.1523/JNEUROSCI.4028-09.2009

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Development/Plasticity/Repair
Retinotopic Mapping Requires Focal Adhesion Kinase-Mediated Regulation of Growth Cone Adhesion

Stephanie Woo,¹ Daniel J. Rowan,² and Timothy M. Gomez²

¹Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, and ²Department of Anatomy and Program in Cellular and Molecular Biology, University of Wisconsin, Madison, Wisconsin 53706

Correspondence should be addressed to Timothy M. Gomez, University of Wisconsin School of Public Health, 257 Bardeen Laboratories, 1300 University Avenue, Madison, WI 53706. Email: tmgomez{at}wisc.edu

Adhesion controls growth cone motility, yet the effects of axon guidance cues on adhesion site dynamics are poorly understood. Here we show that ephrin-A1 reduces retinal ganglion cell (RGC) axon outgrowth by stabilizing existing adhesions and inhibiting new adhesion assembly. Ephrin-A1 activates focal adhesion kinase (FAK) in an integrin- and Src-dependent manner and the effects of ephrin-A1 on growth cone motility require FAK activation. We also find that FAK is expressed in a high temporal to low nasal gradient in RGCs, similar to EphA receptors, and that balanced FAK activation is necessary for optimal axon outgrowth. Last, we find that FAK is required for proper topographic positioning of retinal axons along the anterior–posterior axis of the optic tectum in both Xenopus and zebrafish, a guidance decision mediated in part by A-type ephrins. Together, our data suggest that ephrin-A1 controls growth cone advance by modulating adhesive point contacts through FAK activation and that graded FAK signaling is an important component of ephrin-A-mediated retinotopic mapping.

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Received Aug. 17, 2009; revised Sept. 16, 2009; accepted Sept. 30, 2009.

Correspondence should be addressed to Timothy M. Gomez, University of Wisconsin School of Public Health, 257 Bardeen Laboratories, 1300 University Avenue, Madison, WI 53706. Email: tmgomez{at}wisc.edu

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