Ryk-mediated Wnt repulsion regulates posterior-directed growth of corticospinal tract
Ryk-mediated Wnt repulsion regulates posterior-directed growth of corticospinal tract
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DOI：
10.1038/nn1520
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发表时间：
2005-09-01
影响因子：
25
通讯作者：
Zou, YM
中科院分区：
文献类型：
--
作者：
Liu, YB;Shi, J;Zou, YM
对中枢神经系统纵轴方向的沿着引导线索了解甚少。Wnt蛋白吸引上升的躯体感觉轴突从脊髓投射到大脑。在这里，我们表明，Wnt蛋白排斥皮质脊髓束（CST）轴突在相反的方向。几个Wnt基因被发现在小鼠脊髓灰质中表达，杯状的背索，在一个前到后递减梯度沿沿着颈髓和胸髓。在胶原凝胶分析中，Wnt通过在CST轴突中表达的保守的高亲和力受体Ryk排斥CST轴突。新生儿脊髓以前后分级的方式分泌可扩散的排斥物，其中前脊髓更强，并且排斥活性被Ryk抗体（anti-Ryk）阻断。鞘内注射抗Ryk抗体可阻断CST轴突的后部生长。因此，Wnt蛋白可能在多个类别的轴突的前后引导中具有一般作用。
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.