Slit and Semaphorin signaling governed by Islet transcription factors positions motor neuron somata within the neural tube
Slit and Semaphorin signaling governed by Islet transcription factors positions motor neuron somata within the neural tube
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DOI：
10.1016/j.expneurol.2015.03.024
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发表时间：
2015-07-01
影响因子：
5.3
通讯作者：
Song, Mi-Ryoung
中科院分区：
文献类型：
--
作者：
Lee, Hojae;Kim, Minkyung;Song, Mi-Ryoung
运动神经元向外周肌肉发送轴突，而它们的细胞体留在脊髓腹侧。运动神经元跨越CNS和PNS边界的独特结构可以用边界帽（BC）细胞、基底膜和径向胶质细胞等结构屏障来解释。然而，运动神经元保持其位置的机制尚未得到解决。在这里，我们证明了Islet1 （Isl1）和Islet2 （Isl2）转录因子对运动神经元身份的获得至关重要，也有助于限制神经管内的运动神经元。在缺乏Isl1和Is12的小鼠中，大量的运动神经元离开神经管，甚至在BC细胞出现在腹侧出口点之前。来自Isl1缺失胚胎干细胞的运动神经元的转录谱分析显示，参与排斥机制的主要基因的转录本被错误调控。特别是，在胰岛突变小鼠中，Neuropilinl （Npr1）和Slit2 mRNA的表达减少，这可能是胰岛蛋白的靶基因。与这一机制一致的是，小鼠的Robo和Slit突变以及鸡胚胎中Npr1和Slit2的敲低导致运动神经元向外周迁移。总之，我们的研究表明，胰岛基因参与运动神经元中的Robo-Slit和Neuropilin-Semaphorin信号传导，以保持运动躯体在中枢神经系统内。(C) 2015爱思唯尔公司版权所有。
Motor neurons send out axons to peripheral muscles while their cell bodies remain in the ventral spinal cord. The unique configuration of motor neurons spanning the border between the CNS and PNS has been explained by structural barriers such as boundary cap (BC) cells, basal lamina and radial glia. However, mechanisms in motor neurons that retain their position have not been addressed yet. Here we demonstrate that the Islet1 (Isl1) and Islet2 (Isl2) transcription factors, which are essential for acquisition of motor neuron identity, also contribute to restrict motor neurons within the neural tube. In mice that lack both Isl1 and Is12, large numbers of motor neurons exited the neural tube, even prior to the appearance of BC cells at the ventral exit points. Transcriptional profiling of motor neurons derived from Isl1 null embryonic stem cells revealed that transcripts of major genes involved in repulsive mechanisms were misregulated. Particularly, expression of Neuropilinl (Npr1) and Slit2 mRNA was diminished in Islet mutant mice, and these could be target genes of the Islet proteins. Consistent with this mechanism, Robo and Slit mutations in mice and knockdown of Npr1 and Slit2 in chick embryos caused motor neurons to migrate to the periphery. Together, our study suggests that Islet genes engage Robo-Slit and Neuropilin-Semaphorin signaling in motor neurons to retain motor somata within the CNS. (C) 2015 Elsevier Inc. All rights reserved.