Low Lawrence K, Liu Xiao-Bo, Faulkner Regina L, Coble Jeffrey, Cheng Hwai-Jong
Center for Neuroscience, University of California, Davis, CA 95618, USA.
Proc Natl Acad Sci U S A. 2008 Jun 10;105(23):8136-41. doi: 10.1073/pnas.0803849105. Epub 2008 Jun 3.
Neurons in the developing CNS tend to send out long axon collaterals to multiple target areas. For these neurons to attain specific connections, some of their axon collaterals are subsequently pruned-a process called stereotyped axon pruning. One of the most striking examples of stereotyped pruning in the CNS is the pruning of corticospinal tract (CST) axons. The long CST collaterals from layer V neurons of the visual and motor cortices are differentially pruned during development. Here we demonstrate that select plexins and neuropilins, which serve as coreceptors for semaphorins, are expressed in visual cortical neurons at the time when CST axon collaterals are stereotypically pruned. By analyzing mutant mice, we find that the pruning of visual, but not motor, CST axon collaterals depends on plexin-A3, plexin-A4, and neuropilin-2. Expression pattern study suggests that Sema3F is a candidate local cue for the pruning of visual CST axons. Using electron microscopic analysis, we also show that visual CST axon collaterals form synaptic contacts in the spinal cord before pruning and that the unpruned collaterals in adult mutant mice are unmyelinated and maintain their synaptic contacts. Our results indicate that the stereotyped pruning of the visual and motor CST axon collaterals is differentially regulated and that this specificity arises from the differential expression of plexin receptors in the cortex.
发育中的中枢神经系统中的神经元倾向于向多个目标区域发出长轴突侧支。为了使这些神经元建立特定的连接，它们的一些轴突侧支随后会被修剪——这一过程称为定型轴突修剪。中枢神经系统中定型修剪最显著的例子之一是皮质脊髓束（CST）轴突的修剪。来自视觉和运动皮层V层神经元的长CST侧支在发育过程中被差异性地修剪。在这里，我们证明，作为信号素共受体的特定丛状蛋白和神经纤毛蛋白，在CST轴突侧支进行定型修剪时在视觉皮层神经元中表达。通过分析突变小鼠，我们发现视觉而非运动CST轴突侧支的修剪依赖于丛状蛋白A3、丛状蛋白A4和神经纤毛蛋白2。表达模式研究表明，信号素3F是视觉CST轴突修剪的候选局部信号。通过电子显微镜分析，我们还表明，视觉CST轴突侧支在修剪前在脊髓中形成突触联系，并且成年突变小鼠中未修剪的侧支是无髓鞘的，并维持其突触联系。我们的结果表明，视觉和运动CST轴突侧支的定型修剪受到差异性调节，这种特异性源于皮层中丛状蛋白受体的差异性表达。
