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Ryk-mediated Wnt repulsion regulates posterior-directed growth of corticospinal tract

A Corrigendum to this article was published on 01 January 2006

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Abstract

Guidance cues along the longitudinal axis of the CNS are poorly understood. Wnt proteins attract ascending somatosensory axons to project from the spinal cord to the brain. Here we show that Wnt proteins repel corticospinal tract (CST) axons in the opposite direction. Several Wnt genes were found to be expressed in the mouse spinal cord gray matter, cupping the dorsal funiculus, in an anterior-to-posterior decreasing gradient along the cervical and thoracic cord. Wnts repelled CST axons in collagen gel assays through a conserved high-affinity receptor, Ryk, which is expressed in CST axons. Neonatal spinal cord secretes diffusible repellent(s) in an anterior-posterior graded fashion, with anterior cord being stronger, and the repulsive activity was blocked by antibodies to Ryk (anti-Ryk). Intrathecal injection of anti-Ryk blocked the posterior growth of CST axons. Therefore, Wnt proteins may have a general role in anterior-posterior guidance of multiple classes of axons.

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Figure 1: Anterior-posterior gradient of Wnt expression around the dorsal funiculus.
Figure 2: Wnts repel motor cortical axons.
Figure 3: A repulsive Wnt receptor, Ryk, is expressed on CST axons.
Figure 4: Ryk is required for Wnt1 and Wnt5a repulsion.
Figure 5: Neonatal spinal cord secretes diffusible repellent(s) in an anterior-posterior graded fashion, which can be blocked by anti-Ryk.
Figure 6: Anti-Ryk blocked posterior growth of CST axons in vivo.

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  • 14 December 2005

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Acknowledgements

This work was supported by a Career Development Award from the Schweppe Foundation, Robert Packard ALS Center at Johns Hopkins University, the Brain Research Foundation and the Jack Miller Peripheral Neuropathy Center at the University of Chicago. We thank laboratory members L. King, A. Wolf, A. Schmitt, R. Sherman, J. Chen and A. Fenstermaker for comments and N. Milanesio for help with probes and reagents. We thank F.G. Rathjen for the anti-L1.

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Correspondence to Yimin Zou.

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Supplementary information

Supplementary Fig. 1

Explant assay. (PDF 765 kb)

Supplementary Fig. 2

Methods for quantification of Wnt repulsion (PDF 498 kb)

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Liu, Y., Shi, J., Lu, CC. et al. Ryk-mediated Wnt repulsion regulates posterior-directed growth of corticospinal tract. Nat Neurosci 8, 1151–1159 (2005). https://doi.org/10.1038/nn1520

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