Retinotopic mapping requires focal adhesion kinase-mediated regulation of growth cone adhesion.
Retinotopic mapping requires focal adhesion kinase-mediated regulation of growth cone adhesion.
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DOI：
10.1523/jneurosci.4028-09.2009
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发表时间：
2009-11-04
期刊：
影响因子：
--
通讯作者：
Gomez TM
中科院分区：
文献类型：
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作者：
Woo S;Rowan DJ;Gomez TM
粘附控制生长锥的运动，但对粘附部位动力学轴突导向线索的影响知之甚少。在这里，我们表明，肝配蛋白-A1减少视网膜神经节细胞（RGC）轴突生长稳定现有的粘连和抑制新的粘附组装。肝配蛋白-A1以整合素和Src依赖性方式激活粘着斑激酶（FAK），并且肝配蛋白-A1对生长锥运动性的作用需要FAK激活。我们还发现，FAK在RGCs中以高的颞部到低的鼻梯度表达，类似于EphA受体，并且平衡的FAK激活对于最佳轴突生长是必要的。最后，我们发现，FAK是需要适当的地形定位视网膜轴突沿着视顶盖的前后轴在非洲爪蟾和斑马鱼，一个指导决定介导的部分由A型肝配蛋白。总之，我们的数据表明，肝配蛋白-A1控制生长锥通过调节粘着点接触，通过FAK激活和分级FAK信号是肝配蛋白-A介导的视网膜定位映射的重要组成部分。
Adhesion controls growth cone motility, yet the effects of axon guidance cues on adhesion site dynamics are poorly understood. Here we show that ephrin-A1 reduces retinal ganglion cell (RGC) axon outgrowth by stabilizing existing adhesions and inhibiting new adhesion assembly. Ephrin-A1 activates focal adhesion kinase (FAK) in an integrin- and Src-dependent manner and the effects of ephrin-A1 on growth cone motility require FAK activation. We also find that FAK is expressed in a high temporal to low nasal gradient in RGCs, similar to EphA receptors, and that balanced FAK activation is necessary for optimal axon outgrowth. Last, we find that FAK is required for proper topographic positioning of retinal axons along the anterior–posterior axis of the optic tectum in both Xenopus and zebrafish, a guidance decision mediated in part by A-type ephrins. Together, our data suggest that ephrin-A1 controls growth cone advance by modulating adhesive point contacts through FAK activation and that graded FAK signaling is an important component of ephrin-A-mediated retinotopic mapping.