Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Dev Biol. 2012 Mar 1;363(1):266-78. doi: 10.1016/j.ydbio.2011.12.046. Epub 2012 Jan 8.
As the complexity of animal nervous systems has increased during evolution, developmental control of neuronal connectivity has become increasingly refined. How has functional diversification within related axon guidance molecules contributed to the evolution of nervous systems? To address this question, we explore the evolution of functional diversity within the Roundabout (Robo) family of axon guidance receptors. In Drosophila, Robo and Robo2 promote midline repulsion, while Robo2 and Robo3 specify the position of longitudinal axon pathways. The Robo family has expanded by gene duplication in insects; robo2 and robo3 exist as distinct genes only within dipterans, while other insects, like the flour beetle Tribolium castaneum, retain an ancestral robo2/3 gene. Both Robos from Tribolium can mediate midline repulsion in Drosophila, but unlike the fly Robos cannot be down-regulated by Commissureless. The overall architecture and arrangement of longitudinal pathways are remarkably conserved in Tribolium, despite it having only two Robos. Loss of TcSlit causes midline collapse of axons in the beetle, a phenotype recapitulated by simultaneous knockdown of both Robos. Single gene knockdowns reveal that beetle Robos have specialized axon guidance functions: TcRobo is dedicated to midline repulsion, while TcRobo2/3 also regulates longitudinal pathway formation. TcRobo2/3 knockdown reproduces aspects of both Drosophila robo2 and robo3 mutants, suggesting that TcRobo2/3 has two functions that in Drosophila are divided between Robo2 and Robo3. The ability of Tribolium to organize longitudinal axons into three discrete medial-lateral zones with only two Robo receptors demonstrates that beetle and fly achieve equivalent developmental outcomes using divergent genetic programs.
随着动物神经系统复杂性在进化过程中的增加，神经元连接的发育控制变得越来越精细。在相关的轴突导向分子中，功能多样化是如何促进神经系统的进化的？为了解决这个问题，我们探讨了 Roundabout（Robo）家族轴突导向受体中功能多样性的进化。在果蝇中，Robo 和 Robo2 促进中线排斥，而 Robo2 和 Robo3 决定纵向轴突途径的位置。Robo 家族在昆虫中通过基因复制而扩张；robo2 和 robo3 仅在双翅目昆虫中作为独特的基因存在，而其他昆虫，如面粉甲虫 Tribolium castaneum，则保留了一个祖先的 robo2/3 基因。Tribolium 中的两种 Robos 都可以在果蝇中介导中线排斥，但与果蝇 Robos 不同，它们不能被 Commissureless 下调。尽管 Tribolium 只有两个 Robos，但纵向途径的总体结构和排列在其体内仍然非常保守。TcSlit 的缺失导致甲虫轴突中线崩溃，这一表型与同时敲低两种 Robos 相似。单一基因敲低表明，甲虫 Robos 具有专门的轴突导向功能：TcRobo 专门用于中线排斥，而 TcRobo2/3 还调节纵向途径的形成。TcRobo2/3 敲低再现了果蝇 robo2 和 robo3 突变体的某些方面，这表明 TcRobo2/3 具有两个功能，而在果蝇中，这两个功能分别由 Robo2 和 Robo3 承担。Tribolium 将纵向轴突组织成三个离散的中侧区，仅使用两个 Robo 受体，这表明甲虫和果蝇使用不同的遗传程序实现了等效的发育结果。
