Sabatier Christelle, Plump Andrew S, Brose Katja, Tamada Atsushi, Murakami Fujio, Lee Eva Y-H P, Tessier-Lavigne Marc
Howard Hughes Medical Institute, Department of Anatomy and Department of Biochemistry and Biophysics, The University of California, San Francisco, San Francisco, CA 94143, USA.
Cell. 2004 Apr 16;117(2):157-69. doi: 10.1016/s0092-8674(04)00303-4.
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.
脊椎动物和昆虫中的连合轴突最初会被吸引至神经系统中线，但一旦它们到达这个中间靶点，就会发生显著转变，对中线处的排斥性Slit蛋白产生反应，这些蛋白会将它们驱赶至其轨迹的下一段行程。我们意外地发现，Robo家族的一个不同成员Rig-1（或Robo3）在防止哺乳动物中过早出现Slit敏感性方面发挥作用。连合轴突表达的Rig-1蛋白与Slit敏感性呈负相关。去除Rig-1会导致连合轴突完全无法交叉。遗传和体外分析表明，Rig-1的功能类似于果蝇中的无连合蛋白（Comm），可抑制对Slit的反应性。然而，与Comm不同的是，Rig-1并非通过下调交叉前连合轴突膜上的Robo受体来产生其效应。这些结果确定了一种调节Slit排斥的机制，该机制有助于精心编排轴突在关键中间靶点处从吸引到排斥的精确转变。
