The Wnt receptor Ryk is required for Wnt5a-mediated axon guidance on the contralateral side of the corpus callosum
The Wnt receptor Ryk is required for Wnt5a-mediated axon guidance on the contralateral side of the corpus callosum
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DOI：
10.1523/jneurosci.1175-06.2006
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发表时间：
2006-05-24
影响因子：
5.3
通讯作者：
Cooper, Helen M.
中科院分区：
文献类型：
--
作者：
Keeble, Thomas R.;Halford, Michael M.;Cooper, Helen M.
Ryk（receptor related to tyrosine kinase，酪氨酸激酶相关受体）是秀丽隐杆线虫和果蝇中一种新的Wnt受体。最近，Ryk-Wnt相互作用被证明可以引导皮质脊髓轴突沿着胚胎小鼠脊髓。在这里，我们表明，在Ryk缺陷小鼠，皮质轴突项目异常的主要前脑连合，胼胝体。已经描述了许多小鼠突变体，其中功能丧失突变导致胼胝体轴突不能穿过中线，从而在同侧形成Probst束。与此相反，Ryk的损失不干扰胼胝体轴突的能力，跨越中线，但阻碍他们从中线到对侧逃逸。因此，Ryk（-/-）小鼠表现出一种新的胼胝体引导表型。我们还表明，Wnt 5a作为Ryk的化学排斥配体，驱动胼胝体轴突穿过中线后向对侧半球。此外，而胼胝体轴突跨越中线Ryk（-/-）胚胎，他们是defasciculated同侧，表明Ryk也促进成束的轴突中线交叉前。总之，本研究扩展了Wnt在轴突导向中的新兴作用，并将Ryk确定为胼胝体建立中的关键导向受体。我们对Ryk功能的分析进一步推进了我们对这一重要连合形成的分子机制的理解。
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.