The bone morphogenetic protein roof plate chemorepellent regulates the rate of commissural axonal growth.
The bone morphogenetic protein roof plate chemorepellent regulates the rate of commissural axonal growth.
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DOI：
10.1523/jneurosci.4117-10.2010
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发表时间：
2010-11-17
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影响因子：
--
通讯作者：
Butler SJ
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文献类型：
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作者：
Phan KD;Hazen VM;Frendo M;Jia Z;Butler SJ
连合脊髓轴突响应于骨形态发生蛋白（BMPs）介导的化学排斥而远离顶板（RP）延伸。以前的研究集中在连合轴突的能力，翻译成方向信息的BMP在体外的空间梯度。然而，该系统在体内的一个显著特征是，BMP的梯度被认为是从连合细胞体的后面起作用，使得BMP在连合轴突远离RP生长时对连合轴突具有持续的影响成为可能。在这里，我们证明，骨形成蛋白激活cofilin调节Limk 1控制率的连合轴突在脊髓背侧的延伸。通过调节啮齿动物和鸡连合神经元中的Limk 1活性，轴突生长的速率可以停滞或加速。改变Limk1的激活状态也会影响随后的指导决策：加速轴突在导航其中间目标（地板）时会产生吻尾投射错误。这些结果表明，引导线索可以指定有关生长速度的信息，以确保轴突在发育过程中以特定的时间或速度到达后续信号。
Commissural spinal axons extend away from the roof plate (RP) in response to a chemorepellent mediated by the Bone Morphogenetic Proteins (BMPs). Previous studies have focused on the ability of commissural axons to translate a spatial gradient of BMPs into directional information in vitro. However, a notable feature of this system in vivo is that the gradient of BMPs is thought to act from behind the commissural cell bodies, making it possible for the BMPs to have a continued effect on commissural axons as they grow away from the RP. Here, we demonstrate that BMPs activate the cofilin regulator Limk1 to control the rate of commissural axon extension in the dorsal spinal cord. By modulating Limk1 activity in both rodent and chicken commissural neurons, the rate of axon growth can either be stalled or accelerated. Altering the activation state of Limk1 also influences subsequent guidance decisions: accelerated axons make rostrocaudal projection errors while navigating their intermediate target, the floor plate. These results suggest that guidance cues can specify information about the rate of growth, to ensure that axons reach subsequent signals either at particular times or speeds during development.