Monnier Philippe P, Sierra Ana, Macchi Paolo, Deitinghoff Lutz, Andersen Jens S, Mann Matthias, Flad Manuela, Hornberger Martin R, Stahl Bernd, Bonhoeffer Friedrich, Mueller Bernhard K
Migragen AG, Spemannstrasse 34, 72076 Tuebingen, Germany.
Nature. 2002 Sep 26;419(6905):392-5. doi: 10.1038/nature01041.
Axons rely on guidance cues to reach remote targets during nervous system development. A well-studied model system for axon guidance is the retinotectal projection. The retina can be divided into halves; the nasal half, next to the nose, and the temporal half. A subset of retinal axons, those from the temporal half, is guided by repulsive cues expressed in a graded fashion in the optic tectum, part of the midbrain. Here we report the cloning and functional characterization of a membrane-associated glycoprotein, which we call RGM (repulsive guidance molecule). This molecule shares no sequence homology with known guidance cues, and its messenger RNA is distributed in a gradient with increasing concentration from the anterior to posterior pole of the embryonic tectum. Recombinant RGM at low nanomolar concentration induces collapse of temporal but not of nasal growth cones and guides temporal retinal axons in vitro, demonstrating its repulsive and axon-specific guiding activity.
在神经系统发育过程中，轴突依靠导向线索到达远处的靶标。一个被充分研究的轴突导向模型系统是视网膜 - 脑顶盖投射。视网膜可分为两半：靠近鼻子的鼻侧半和颞侧半。视网膜轴突的一个子集，即来自颞侧半的轴突，受中脑部分的视顶盖中以梯度方式表达的排斥性线索引导。在此，我们报告了一种膜相关糖蛋白的克隆及功能特性，我们将其称为RGM（排斥性导向分子）。该分子与已知的导向线索没有序列同源性，其信使核糖核酸以梯度形式分布，从胚胎脑顶盖的前极到后极浓度逐渐增加。低纳摩尔浓度的重组RGM可诱导颞侧而非鼻侧生长锥塌陷，并在体外引导颞侧视网膜轴突，证明了其排斥性和轴突特异性导向活性。
