The divergent Robo family protein Rig-1/Robo3 is a negative regulator of slit responsiveness required for midline crossing by commissural axons
The divergent Robo family protein Rig-1/Robo3 is a negative regulator of slit responsiveness required for midline crossing by commissural axons
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DOI：
10.1016/s0092-8674(04)00303-4
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发表时间：
2004-04-16
期刊：
影响因子：
64.5
通讯作者：
Tessier-Lavigne, M
中科院分区：
文献类型：
--
作者：
Sabatier, C;Plump, AS;Tessier-Lavigne, M
脊椎动物和昆虫的连合轴突最初被吸引到神经系统中线，但一旦它们到达这个中间目标，它们就会发生戏剧性的转变，对中线的排斥性Slit蛋白产生反应，将它们驱逐到下一条轨道。我们意外地发现了Robo家族的一个不同成员Rig-1（或Robo 3），它可以预防哺乳动物过早的Slit敏感性。连合轴突的Rig-1蛋白表达与Slit敏感性呈负相关。移除Rig-1导致连合轴突完全无法穿过。遗传和体外分析表明，Rig-1的功能抑制Slit响应类似于果蝇中的Commissuerless（Comm）。然而，与Comm不同，Rig-1并不通过下调交叉前连合轴突膜上的Robo受体来产生其作用。这些结果确定了一种调节Slit排斥的机制，该机制有助于在关键的中间轴突目标处设计从吸引到排斥的精确切换。
Commissural axons in vertebrates and insects are initially attracted to the nervous system midline, but once they reach this intermediate target they undergo a dramatic switch, becoming responsive to repellent Slit proteins at the midline, which expel them onto the next leg of their trajectory. We have unexpectedly implicated a divergent member of the Robo family, Rig-1 (or Robo3), in preventing premature Slit sensitivity in mammals. Expression of Rig-1 protein by commissural axons is inversely correlated with Slit sensitivity. Removal of Rig-1 results in a total failure of commissural axons to cross. Genetic and in vitro analyses indicate that Rig-1 functions to repress Slit responsiveness similarly to Commissureless (Comm) in Drosophila. Unlike Comm, however, Rig-1 does not produce its effect by downregulating Robo receptors on precrossing commissural axon membranes. These results identify a mechanism for regulating Slit repulsion that helps choreograph the precise switch from attraction to repulsion at a key intermediate axonal target.