Pioneer longitudinal axons navigate using floor plate and Slit/Robo signals
Pioneer longitudinal axons navigate using floor plate and Slit/Robo signals
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DOI：
10.1242/dev.023325
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发表时间：
2008-11-15
期刊：
影响因子：
4.6
通讯作者：
Mastick, Grant S.
中科院分区：
文献类型：
--
作者：
Farmer, W. Todd;Altick, Amy L.;Mastick, Grant S.
纵向轴突在大脑和脊髓之间传递所有信号。它们穿过脑干的轴突束是由一组简单的先锋轴突建立起来的，这些轴突具有与底板平行的精确轨迹。为了确定体内的纵向引导机制，测试了底板组织的总体作用和Sit/Robo信号的特定作用。异位诱导或底板基因缺失使纵向轴突转向异常轨迹。在底板实验中，缝隙家族可扩散线索的表达模式发生了变化，表明它们参与了纵向引导。对Slit1和Slit2及其受体Robo1和Robo2在突变小鼠中进行了遗传检测。Slit1；Slit2双突变体有严重的纵向错误，特别是腹侧轴突，包括中线交叉和漂移的纵向轨迹。Robo1和Robo2在很大程度上是基因冗余的，似乎都没有具体说明特定的区域位置。然而，Robo1和Robo2联合突变强烈扰乱了每个先锋区域。因此，先锋轴突依赖于远距离的底板信号，而Sit/Robo信号是精确的纵向轨迹所必需的。
Longitudinal axons transmit all signals between the brain and spinal cord. Their axon tracts through the brain stem are established by a simple set of pioneer axons with precise trajectories parallel to the floor plate. To identify longitudinal guidance mechanisms in vivo, the overall role of floor plate tissue and the specific roles of Slit/Robo signals were tested. Ectopic induction or genetic deletion of the floor plate diverted longitudinal axons into abnormal trajectories. The expression patterns of the diffusible cues of the Slit family were altered in the floor plate experiments, suggesting their involvement in longitudinal guidance. Genetic tests of Slit1 and Slit2, and the Slit receptors Robo1 and Robo2 were carried out in mutant mice. Slit1; Slit2 double mutants had severe longitudinal errors, particularly for ventral axons, including midline crossing and wandering longitudinal trajectories. Robo1 and Robo2 were largely genetically redundant, and neither appeared to specify specific tract positions. However, combined Robo1 and Robo2 mutations strongly disrupted each pioneer tract. Thus, pioneer axons depend on long-range floor plate cues, with Slit/Robo signaling required for precise longitudinal trajectories.