ROBO directs axon crossing of segmental boundaries by suppressing responsiveness to relocalized Netrin
ROBO directs axon crossing of segmental boundaries by suppressing responsiveness to relocalized Netrin
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DOI：
10.1038/nn1612
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发表时间：
2006-01-01
影响因子：
25
通讯作者：
Hiromi, Y
中科院分区：
文献类型：
--
作者：
Hiramoto, M;Hiromi, Y
中枢神经系统中的网络由以重复阵列连接的神经模块组成。尽管各个模块包含轴突在单元内跟踪的指导信息，但这些指导线索阻碍了轴突跨模块边界的延伸。我们通过分析果蝇神经节的纵向连接来研究轴突如何解决这个“边界问题”。纵向轴突的初始轨迹由 Netrin 引导，Netrin 通过其受体 Frazzled 定位在连合轴突上。下一段连合处的 Netrin 提示可以充当纵向轴突的屏障，抑制其延伸并沿着连合误导它们向对侧延伸。我们发现，在到达节段边界之前，纵向轴突对连合处出现的 Netrin 的反应被 Roundabout (ROBO) 通过抵消 Gq 信号传导而抑制。缺乏抑制会导致机器人表型：纵向轴突向中线突出，就像绕着环形交叉口（旋转）运行一样。
Networks in the CNS consist of neural modules that are connected in a repetitive array. Whereas individual modules contain guidance information along which axons track within the unit, these guidance cues hinder axon extension across module boundaries. We investigated how axons solve this 'boundary problem' by analyzing the longitudinal connections of neuromeres in Drosophila melanogaster. The initial trajectory of the longitudinal axons is guided by Netrin, which is localized on commissural axons by its receptor, Frazzled. The Netrin cue on the commissure of the next segment can act as a barrier to longitudinal axons, inhibiting their extension and misguiding them contralaterally along the commissure. We show that, before reaching the segmental boundary, the longitudinal axons' responsiveness to Netrin presented on the commissure is suppressed by Roundabout (ROBO), through counteracting Gq signaling. The absence of suppression causes the robo phenotype: longitudinal axons project toward the midline, as if running around a roundabout (rotary).