Robo1 and Robo2 control the development of the lateral olfactory tract
Robo1 and Robo2 control the development of the lateral olfactory tract
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DOI：
10.1523/jneurosci.0172-07.2007
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发表时间：
2007-03-14
影响因子：
5.3
通讯作者：
Nguyen-Ba-Charvet, Kim T.
中科院分区：
文献类型：
--
作者：
Fouquet, Coralie;Di Meglio, Thomas;Nguyen-Ba-Charvet, Kim T.
形成外侧嗅束（LOT）的嗅球投射的发育仍然知之甚少。已知隔分泌Slit 1和Slit 2，其在体外排斥嗅觉轴突，并且在Slit 1（-/-）; Slit 2（-/-）突变小鼠中，LOT被严重破坏。然而，参与Slit受体，迂回（Robo）蛋白，在引导LOT轴突尚未得到证实。我们在这里表明，Robo 1和Robo 2受体都表达在早期发展的LOT轴突，但只有Robo 2是目前在以后的发展阶段。来自Robo 1（-/-）; Robo 2（-/-）双突变小鼠的嗅球轴突在体外不被Slit排斥。LOT在Robo 1（-/-）小鼠中正常发育，但在Robo 2（-/-）和Robo 1（-/-）; Robo 2（-/-）双突变胚胎中完全紊乱，许多LOT轴突沿着端脑的腹侧表面伸展。最后，在Slit 1（-/-）; Slit 2（-/-）小鼠和Robo 1（-/-）; Robo 2（-/-）小鼠中，被认为是LOT路标细胞的lot 1表达细胞的位置似乎未受影响。总之，我们的研究结果表明，Robo 1和Robo 2直接介导LOT轴突上Slit受体的排斥活性，并且是体内这些轴突正常引导所必需的。
The development of olfactory bulb projections that form the lateral olfactory tract (LOT) is still poorly understood. It is known that the septum secretes Slit1 and Slit2 which repel olfactory axons in vitro and that in Slit1(-/-); Slit2(-/-) mutant mice, the LOT is profoundly disrupted. However, the involvement of Slit receptors, the roundabout (Robo) proteins, in guiding LOT axons has not been demonstrated. We show here that both Robo1 and Robo2 receptors are expressed on early developing LOT axons, but that only Robo2 is present at later developmental stages. Olfactory bulb axons from Robo1(-/-); Robo2(-/-) double-mutant mice are not repelled by Slit in vitro. The LOT develops normally in Robo1(-/-) mice, but is completely disorganized in Robo2(-/-) and Robo1(-/-); Robo2(-/-) double-mutant embryos, with many LOT axons spreading along the ventral surface of the telencephalon. Finally, the position of lot1-expressing cells, which have been proposed to be the LOT guidepost cells, appears unaffected in Slit1(-/-); Slit2(-/-) mice and in Robo1(-/-); Robo2(-/-) mice. Together, our results indicate that Robo1 and Robo2 directly mediate the repulsive activity of Slit receptors on LOT axons, and are required for normal guidance of these axons in vivo.