Slit-mediated repulsion is a key regulator of motor axon pathfinding in the hindbrain
Slit-mediated repulsion is a key regulator of motor axon pathfinding in the hindbrain
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DOI：
10.1242/dev.02038
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发表时间：
2005-10-01
期刊：
影响因子：
4.6
通讯作者：
Guthrie, S
中科院分区：
文献类型：
--
作者：
Hammond, R;Vivancos, V;Guthrie, S
底板被认为是颅运动轴突的排斥信号来源，阻止它们穿过后脑中线。然而，尚不清楚哪些分子在体内介导这种效应。我们表明，Slit和Robo蛋白是候选运动轴突引导分子，因为Robo蛋白由颅运动神经元表达，Slit蛋白由限定运动轴突轨迹的组织表达，即底板和菱形唇。我们目前在体外的证据表明，Slit1和Slit2蛋白是选择性的抑制剂和排斥剂的背侧投射，但不是腹侧投射，颅运动轴突。对Slit和Robo功能缺陷小鼠的分析表明，颅运动轴突异常进入中线，而鸡胚中Slit1的异位表达导致特定的运动轴突投射错误。显性负性Robo受体在鸡胚颅运动神经元内的表达显著地扰乱了它们的投射，导致一些运动轴突进入中线，并阻止背侧投射的运动轴突离开后脑。这些数据表明，Slit蛋白在引导背侧投射的颅运动神经元和促进其神经管出口中起着关键作用。
The floor plate is known to be a source of repellent signals for cranial motor axons, preventing them from crossing the midline of the hindbrain. However, it is unknown which molecules mediate this effect in vivo. We show that Slit and Robo proteins are candidate motor axon guidance molecules, as Robo proteins are expressed by cranial motoneurons, and Slit proteins are expressed by the tissues that delimit motor axon trajectories, i.e. the floor plate and the rhombic lip. We present in vitro evidence showing that Slit1 and Slit2 proteins are selective inhibitors and repellents for dorsally projecting, but not for ventrally projecting, cranial motor axons. Analysis of mice deficient in Slit and Robo function shows that cranial motor axons aberrantly enter the midline, while ectopic expression of Slit1 in chick embryos leads to specific motor axon projection errors. Expression of dominant-negative Robo receptors within cranial motoneurons in chick embryos strikingly perturbs their projections, causing some motor axons to enter the midline, and preventing dorsally projecting motor axons from exiting the hindbrain. These data suggest that Slit proteins play a key role in guiding dorsally projecting cranial motoneurons and in facilitating their neural tube exit.