Yampolsky Pessah, Gensler Sven, McArdle Joseph, Witzemann Veit
Max-Planck-Institute for Medical Research, Department of Cell Physiology, Jahnstrasse 29, D-69120 Heidelberg, Germany.
Mol Cell Neurosci. 2008 Mar;37(3):634-45. doi: 10.1016/j.mcn.2007.12.014. Epub 2007 Dec 15.
We generated knock-in mice that express GFP-labeled embryonic-type acetylcholine receptors (AChR) to follow postsynaptic differentiation and innervation during embryonic development and to visualize the postnatally occurring channel conversion from embryonic- to adult-type AChR. The dynamics of AChRgamma/AChRepsilon conversion at the neuromuscular junction indicates that muscle-specific programs of receptor subunit gene transcription control AChR replacement. While conversion proceeds from peripheral to central regions for individual endplates, it does not occur simultaneously for all endplates. Although GFP-labeled receptors were expressed at reduced levels, the localization of postsynaptic sites and synapse formation was not noticeably altered. However, these alterations correlated with a striking reduction of motoneuron programmed cell death, transient increase of neurite growth and axon branching. This animal model refines the view on reciprocal neuromuscular signaling and suggests that motoneuron survival and axon branching are directly regulated by AChR function to enable optimal innervation and timing of neurally evoked muscle contraction.
我们生成了表达绿色荧光蛋白（GFP）标记的胚胎型乙酰胆碱受体（AChR）的基因敲入小鼠，以追踪胚胎发育过程中突触后分化和神经支配情况，并观察出生后发生的从胚胎型AChR到成年型AChR的通道转换。神经肌肉接头处AChRγ/AChRε转换的动力学表明，受体亚基基因转录的肌肉特异性程序控制着AChR的替换。虽然对于单个终板而言，转换是从周边区域向中央区域进行的，但并非所有终板同时发生转换。尽管GFP标记的受体表达水平降低，但突触后位点的定位和突触形成并未明显改变。然而，这些改变与运动神经元程序性细胞死亡的显著减少、神经突生长和轴突分支的短暂增加相关。该动物模型完善了对神经肌肉相互信号传导的认识，并表明运动神经元的存活和轴突分支直接受AChR功能调控，以实现神经诱发肌肉收缩的最佳神经支配和时机。
