Research Institute of Molecular Pathology, Dr. Bohr-gasse 7, A-1030 Vienna, Austria.
Cell. 2010 Feb 5;140(3):409-20. doi: 10.1016/j.cell.2010.01.002.
The orthogonal array of axon pathways in the Drosophila CNS is constructed in part under the control of three Robo family axon guidance receptors: Robo1, Robo2 and Robo3. Each of these receptors is responsible for a distinct set of guidance decisions. To determine the molecular basis for these functional specializations, we used homologous recombination to create a series of 9 "robo swap" alleles: expressing each of the three Robo receptors from each of the three robo loci. We demonstrate that the lateral positioning of longitudinal axon pathways relies primarily on differences in gene regulation, not distinct combinations of Robo proteins as previously thought. In contrast, specific features of the Robo1 and Robo2 proteins contribute to their distinct functions in commissure formation. These specializations allow Robo1 to prevent crossing and Robo2 to promote crossing. These data demonstrate how diversification of expression and structure within a single family of guidance receptors can shape complex patterns of neuronal wiring.
果蝇中枢神经系统中的轴突通路的正交排列部分是由三种 Robo 家族轴突导向受体（Robo1、Robo2 和 Robo3）控制构建的。这三种受体各自负责一组不同的导向决策。为了确定这些功能特化的分子基础，我们使用同源重组创建了一系列 9 个“robo 交换”等位基因：从三个 Robo 基因座中的每一个表达三种 Robo 受体。我们证明，纵向轴突通路的侧向定位主要依赖于基因调控的差异，而不是以前认为的 Robo 蛋白的不同组合。相比之下，Robo1 和 Robo2 蛋白的特定特征有助于它们在连接形成中的不同功能。这些特化使 Robo1 能够阻止交叉，而 Robo2 则促进交叉。这些数据表明，在单个导向受体家族内的表达和结构多样化如何能够塑造复杂的神经元连接模式。
