Wnt5a induces simultaneous cortical axon outgrowth and repulsive axon guidance through distinct signaling mechanisms.
Wnt5a induces simultaneous cortical axon outgrowth and repulsive axon guidance through distinct signaling mechanisms.
复制标题
DOI：
10.1523/jneurosci.0183-09.2009
复制
发表时间：
2009-05-06
期刊：
影响因子：
--
通讯作者：
Kalil K
中科院分区：
文献类型：
--
作者：
Li L;Hutchins BI;Kalil K
wnt是形态因子，也起着轴突引导分子的作用。在体内，通过Ryk受体的Wnt5a梯度被发现排斥皮质轴突进入胼胝体和皮质脊髓通路。在这里，使用分离的皮质培养物，我们发现使用Wnt5a可以增加轴突的生长。在转向实验中，Wnt5a梯度同时增加轴突生长并诱导排斥转向，这是体内皮层轴突推进的一种潜在机制。我们发现轴突的生长是由Ryk介导的，而轴突排斥需要Ryk和Frizzled受体。这两种受体介导Wnt引起的细胞内钙的波动，这是Wnt5a增加轴突生长和排斥所必需的。然而，轴突生长的增加涉及钙通过IP3受体从储存中释放，以及钙通过TRP通道流入，轴突排斥是由TRP通道介导的，而不涉及IP3受体。这些结果揭示了Wnt5a诱导轴突生长和排斥引导的不同信号机制。
Wnts are morphogens that also function as axon guidance molecules. In vivo Wnt5a gradients via Ryk receptors were found to repel cortical axons into developing callosal and corticospinal pathways. Here, using dissociated cortical cultures, we found that bath applied Wnt5a increased axon outgrowth. In turning assays Wnt5a gradients simultaneously increased axon outgrowth and induced repulsive turning, a potential mechanism for propelling cortical axons in vivo. We found that axon outgrowth is mediated by Ryk whereas axon repulsion requires both Ryk and Frizzled receptors. Both receptors mediate Wnt evoked fluctuations in intracellular calcium, which is required for increased axon outgrowth and repulsion by Wnt5a. However, whereas increased axon outgrowth involves calcium release from stores through IP3 receptors as well as calcium influx through TRP channels, axon repulsion is mediated by TRP channels without involvement of IP3 receptors. These results reveal distinct signaling mechanisms underlying Wnt5a induced axon outgrowth and repulsive guidance.