RT Journal Article
SR Electronic
T1 The Wnt Receptor Ryk Is Required for Wnt5a-Mediated Axon Guidance on the Contralateral Side of the Corpus Callosum
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5840
OP 5848
DO 10.1523/JNEUROSCI.1175-06.2006
VO 26
IS 21
A1 Thomas R. Keeble
A1 Michael M. Halford
A1 Clare Seaman
A1 Nigel Kee
A1 Maria Macheda
A1 Richard B. Anderson
A1 Steven A. Stacker
A1 Helen M. Cooper
YR 2006
UL http://www.jneurosci.org/content/26/21/5840.abstract
AB 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.