Ng Julian, Nardine Timothy, Harms Matthew, Tzu Julia, Goldstein Ann, Sun Yan, Dietzl Georg, Dickson Barry J, Luo Liqun
Department of Biological Sciences, Stanford University, Stanford, California 94305, USA.
Nature. 2002 Mar 28;416(6879):442-7. doi: 10.1038/416442a.
Growth, guidance and branching of axons are all essential processes for the precise wiring of the nervous system. Rho family GTPases transduce extracellular signals to regulate the actin cytoskeleton. In particular, Rac has been implicated in axon growth and guidance. Here we analyse the loss-of-function phenotypes of three Rac GTPases in Drosophila mushroom body neurons. We show that progressive loss of combined Rac1, Rac2 and Mtl activity leads first to defects in axon branching, then guidance, and finally growth. Expression of a Rac1 effector domain mutant that does not bind Pak rescues growth, partially rescues guidance, but does not rescue branching defects of Rac mutant neurons. Mosaic analysis reveals both cell autonomous and non-autonomous functions for Rac GTPases, the latter manifesting itself as a strong community effect in axon guidance and branching. These results demonstrate the central role of Rac GTPases in multiple aspects of axon development in vivo, and suggest that axon growth, guidance and branching could be controlled by differential activation of Rac signalling pathways.
轴突的生长、导向和分支是神经系统精确布线的所有基本过程。Rho家族小G蛋白将细胞外信号转导以调节肌动蛋白细胞骨架。特别是，Rac已被证明与轴突生长和导向有关。在这里，我们分析了果蝇蘑菇体神经元中三种Rac小G蛋白的功能丧失表型。我们表明，Rac1、Rac2和Mtl活性的逐渐丧失首先导致轴突分支缺陷，然后是导向缺陷，最后是生长缺陷。不结合Pak的Rac1效应结构域突变体的表达挽救了生长，部分挽救了导向，但没有挽救Rac突变神经元的分支缺陷。嵌合体分析揭示了Rac小G蛋白的细胞自主和非自主功能，后者在轴突导向和分支中表现为强烈的群体效应。这些结果证明了Rac小G蛋白在体内轴突发育多个方面的核心作用，并表明轴突生长、导向和分支可能由Rac信号通路的差异激活来控制。
