Roundabout 2 regulates migration of sensory neurons by signaling in trans
Roundabout 2 regulates migration of sensory neurons by signaling in trans
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DOI：
10.1016/j.cub.2004.07.052
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发表时间：
2004-08-10
期刊：
影响因子：
9.2
通讯作者：
Zinn, K
中科院分区：
文献类型：
--
作者：
Kraut, R;Zinn, K
背景：Roundabout（Robo）受体及其配体Slit是轴突导向和细胞迁移的重要调节因子。果蝇胚胎感觉器官的发展提供了一个神经元迁移的范例，在体内的角色的狭缝和机器人可以使用genetics.Results：在这里，我们表明，狭缝机器人信号控制果蝇幼虫的感觉神经元的部分弦音（Cho）拉伸受体器官的迁移。我们使用的实时成像显示，腹部Cho器官通常迁移腹在发展过程中，而胸部Cho器官不。Robo 2顺式（感觉神经元）或反式（相邻内脏中胚层）过表达通过阻断迁移将腹部器官转化为胸部形态和位置，而Slit-Robo信号传导的丧失产生了胸部器官异位迁移的反向转化。救援和组织特异性敲除实验表明，由Robo 2的反式信号有助于胸部Cho器官的正常定位。Cho器官在胸部和腹部之间的差异定位已知是由Hox基因调控的，我们发现，Hox的重要辅因子Homothorax抑制了腹部内脏中胚层中Robo 2的表达。我们的研究结果表明，节段特异性神经元迁移模式是通过一种新的信号复合物（“Slit三明治”），其中胸内脏中胚层上的Robo 2与Slit结合并将其呈递给Cho神经元上的Robo受体。Cho器官在胸部和腹部之间的差异定位可以通过Hox基因介导的robo 2抑制来确定。
Background: Roundabout (Robo) receptors and their ligand Slit are important regulators of axon guidance and cell migration. The development of Drosophila embryonic sense organs provides a neuronal migration paradigm where the in vivo roles of Slit and Robo can be assayed using genetics.Results: Here we show that Slit-Robo signaling controls migration of Drosophila larval sensory neurons that are part of the Chordotonal (Cho) stretch receptor organs. We used live imaging to show that abdominal Cho organs normally migrate ventrally during development, whereas thoracic Cho organs do not. Robo2 overexpression in cis (in the sensory neurons) or in trans (on neighboring visceral mesoderm) transforms abdominal organs to a thoracic morphology and position by blocking migration, while loss of Slit-Robo signaling produces a reverse transformation in which thoracic organs migrate ectopically. Rescue and tissue-specific knockout experiments indicate that trans signaling by Robo2 contributes to the normal positioning of the thoracic Cho organs. The differential positioning of Cho organs between the thorax and abdomen is known to be regulated by Hox genes, and we show that the essential Hox cofactor Homothorax, represses Robo2 expression in the abdominal visceral mesoderm.Conclusions: Our results suggest that segment-specific neuronal migration patterns are directed through a novel signaling complex (the "Slit sandwich") in which Robo2 on the thoracic visceral mesoderm binds to Slit and presents it to Robo receptors on Cho neurons. The differential positioning of Cho organs between thorax and abdomen may be determined by Hox gene-mediated repression of robo2.