Neuroscience Graduate Program, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089, USA.
J Neurosci. 2010 Nov 17;30(46):15430-40. doi: 10.1523/JNEUROSCI.4117-10.2010.
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 Lim domain kinase 1 (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.
连合脊髓轴突在骨形态发生蛋白（BMPs）介导的化学排斥物的作用下，从顶板（RP）延伸出来。先前的研究集中在连合轴突将 BMPs 的空间梯度转化为体外定向信息的能力上。然而，该系统在体内的一个显著特征是，BMPs 梯度被认为是从连合细胞体的后面起作用的，这使得 BMPs 有可能在连合轴突远离 RP 生长的过程中对其产生持续的影响。在这里，我们证明 BMPs 通过激活丝切蛋白调节激酶 1（Limk1）来控制背侧脊髓中连合轴突的延伸速度。通过调节啮齿动物和鸡连合神经元中的 Limk1 活性，可以使轴突生长速度停滞或加速。改变 Limk1 的激活状态也会影响后续的导向决策：加速的轴突在导航其中间目标——基板时，会出现前后投射错误。这些结果表明，导向线索可以指定关于生长速度的信息，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。
