Rusan Nasser M, Akong Kathryn, Peifer Mark
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
J Cell Biol. 2008 Oct 20;183(2):203-12. doi: 10.1083/jcb.200807079. Epub 2008 Oct 13.
The highly polarized architecture of neurons is important for their function. Experimental data based on dominant-negative approaches suggest that the tumor suppressor adenomatous polyposis coli (APC), a regulator of Wnt signaling and the cytoskeleton, regulates polarity of neuroectodermal precursors and neurons, helping specify one neurite as the axon, promoting its outgrowth, and guiding axon pathfinding. However, such dominant-negative approaches might affect processes in which APC is not essential. We completely removed both APCs from Drosophila melanogaster larval neural precursors and neurons, testing whether APCs play universal roles in neuronal polarity. Surprisingly, APCs are not essential for asymmetric cell division or the stereotyped division axis of central brain (CB) neuroblasts, although they do affect cell cycle progression and spindle architecture. Likewise, CB, lobular plug, and mushroom body neurons do not require APCs for polarization, axon outgrowth, or, in the latter two cases, axon targeting. These data suggest that proposed cytoskeletal roles for APCs in mammals should be reassessed using loss of function tools.
神经元高度极化的结构对其功能至关重要。基于显性负性方法的实验数据表明，肿瘤抑制因子腺瘤性息肉病基因（APC）作为Wnt信号和细胞骨架的调节因子，调控神经外胚层前体细胞和神经元的极性，有助于将一条神经突指定为轴突，促进其生长，并引导轴突寻路。然而，这种显性负性方法可能会影响APC并非必不可少的过程。我们从黑腹果蝇幼虫神经前体细胞和神经元中完全去除了两个APC基因，以测试APC基因在神经元极性中是否发挥普遍作用。令人惊讶的是，APC基因对于中枢脑（CB）神经母细胞的不对称细胞分裂或定型分裂轴并非必不可少，尽管它们确实会影响细胞周期进程和纺锤体结构。同样，CB神经元、小叶栓神经元和蘑菇体神经元在极化、轴突生长方面，或者在后两种情况下的轴突靶向方面都不需要APC基因。这些数据表明，应该使用功能丧失工具重新评估在哺乳动物中提出的APC基因在细胞骨架方面的作用。
