Alternative splicing of the Robo3 axon guidance receptor governs the midline switch from attraction to repulsion
Alternative splicing of the Robo3 axon guidance receptor governs the midline switch from attraction to repulsion
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DOI：
10.1016/j.neuron.2008.02.016
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发表时间：
2008-05-08
期刊：
影响因子：
16.2
通讯作者：
Tessier-Lavigne, Marc
中科院分区：
文献类型：
--
作者：
Chen, Zhe;Gore, Bryan B.;Tessier-Lavigne, Marc
选择性剪接提供了一种手段，以增加基因功能的复杂性，在许多生物过程中，包括神经系统布线。导航轴突对中间目标的反应从吸引转变为排斥，使它们能够生长到每个中间目标，然后继续前进。我们以前表明，Slit受体Robo3需要脊髓连合轴突进入和穿越中线中间目标。我们在这里报告存在两个功能拮抗亚型的Robo3不同的羧基末端产生的选择性剪接。Robo3.1部署在连合轴突的交叉前和交叉部分，并通过抑制缝隙排斥来允许中线交叉。Robo3.2在后交叉部分表达，并阻止中线再交叉，有利于Slit排斥。对手剪接变体的紧密空间调节有助于确保轴突反应在中线处从吸引到排斥的高保真度过渡。
Alternative splicing provides a means to increase the complexity of gene function in numerous biological processes, including nervous system wiring. Navigating axons switch responses from attraction to repulsion at intermediate targets, allowing them to grow to each intermediate target and then to move on. The mechanisms underlying this switch remain poorly characterized. We previously showed that the Slit receptor Robo3 is required for spinal commissural axons to enter and cross the midline intermediate target. We report here the existence of two functionally antagonistic isoforms of Robo3 with distinct carboxy termini arising from alternative splicing. Robo3.1 is deployed on the precrossing and crossing portions of commissural axons and allows midline crossing by silencing Slit repulsion. Robo3.2 becomes expressed on the postcrossing portion and blocks midline recrossing, favoring Slit repulsion. The tight spatial regulation of opponent splice variants helps ensure high-fidelity transition of axonal responses from attraction to repulsion at the midline.