The Wnt receptor Ryk is required for Wnt5a-mediated axon guidance on the contralateral side of the corpus callosum

Keeble, T. R., Halford, M., Seaman, C., Kee, N., Macheda, M., Andersen, R. B., Stacker, S. A. and Cooper, H. M. (2006) The Wnt receptor Ryk is required for Wnt5a-mediated axon guidance on the contralateral side of the corpus callosum. Journal of Neuroscience, 26 21: 5840-5848. doi:10.1523/JNEUROSCI.1175-06.2006

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Author Keeble, T. R.
Halford, M.
Seaman, C.
Kee, N.
Macheda, M.
Andersen, R. B.
Stacker, S. A.
Cooper, H. M.
Title The Wnt receptor Ryk is required for Wnt5a-mediated axon guidance on the contralateral side of the corpus callosum
Journal name Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
Publication date 2006
Sub-type Article (original research)
DOI 10.1523/JNEUROSCI.1175-06.2006
Open Access Status File (Publisher version)
Volume 26
Issue 21
Start page 5840
End page 5848
Total pages 9
Editor D. C. Van Essen
Place of publication Washington, DC, USA
Publisher Society for Neuroscience
Collection year 2006
Language eng
Subject C1
320702 Central Nervous System
730104 Nervous system and disorders
Abstract Ryk (receptor related to tyrosine kinase) has been shown to be a novel Wnt receptor in both Caenorhabditis elegans and Drosophila melanogaster. Recently, Ryk-Wnt interactions were shown to guide corticospinal axons down the embryonic mouse spinal cord. Here we show that, in Ryk-deficient mice, cortical axons project aberrantly across the major forebrain commissure, the corpus callosum. Many mouse mutants have been described in which loss-of-function mutations result in the inability of callosal axons to cross the midline, thereby forming Probst bundles on the ipsilateral side. In contrast, loss of Ryk does not interfere with the ability of callosal axons to cross the midline but impedes their escape from the midline into the contralateral side. Therefore, Ryk(-/-) mice display a novel callosal guidance phenotype. We also show that Wnt5a acts as a chemorepulsive ligand for Ryk, driving callosal axons toward the contralateral hemisphere after crossing the midline. In addition, whereas callosal axons do cross the midline in Ryk(-/-) embryos, they are defasciculated on the ipsilateral side, indicating that Ryk also promotes fasciculation of axons before midline crossing. In summary, this study expands the emerging role for Wnts in axon guidance and identifies Ryk as a key guidance receptor in the establishment of the corpus callosum. Our analysis of Ryk function further advances our understanding of the molecular mechanisms underlying the formation of this important commissure.
Keyword axon guidance
corpus callosum
Ryk receptor
loss-of-function
Wnt5a
chemorepulsion
Drosophila Derailed Receptor
Differentiation
Slit
Q-Index Code C1

 
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Created: Wed, 15 Aug 2007, 09:24:22 EST