Van Essen D C, Gordon H, Soha J M, Fraser S E
Biology Division, Caltech, Pasadena, California.
J Neurobiol. 1990 Jan;21(1):223-49. doi: 10.1002/neu.480210115.
During development, the neuromuscular junction passes through a stage of extensive polyinnervation followed by a period of wholesale synapse elimination. In this report we discuss mechanisms and interactions that could mediate many of the key aspects of these important developmental events. Our emphasis is on (1) establishing an overall conceptual framework within which the role of many distinct cellular interactions and molecular factors can be evaluated, and (2) generating computer simulations that systematically test the adequacy of different models in accounting for a wide range of biological data. Our analysis indicates that several relatively simple mechanisms are each capable of explaining a variety of experimental observations. On the other hand, no one mechanism can account for the full spectrum of experimental results. Thus, it is important to consider models that are based on interactions among multiple mechanisms. A potentially powerful combination is one based on (1) a scaffold within the basal lamina or in the postsynaptic membrane which is induced by nerve terminals and which serves to stabilize terminals by a positive feedback mechanism; (2) a sprouting factor whose release by muscle fibers is down-regulated by activity and perhaps other factors; and (3) an intrinsic tendency of motor neurons to withdraw some connections while allowing others to grow.
在发育过程中，神经肌肉接头会经历一个广泛多神经支配的阶段，随后是一个大规模突触消除的时期。在本报告中，我们讨论了可能介导这些重要发育事件许多关键方面的机制和相互作用。我们的重点是：（1）建立一个总体概念框架，在其中可以评估许多不同细胞相互作用和分子因素的作用；（2）生成计算机模拟，系统地测试不同模型在解释广泛生物数据方面的充分性。我们的分析表明，几种相对简单的机制各自都能够解释各种实验观察结果。另一方面，没有一种机制能够解释全部实验结果。因此，考虑基于多种机制相互作用的模型很重要。一种潜在强大的组合是基于：（1）基膜内或突触后膜中的一种支架，它由神经末梢诱导产生，并通过正反馈机制来稳定末梢；（2）一种由肌纤维释放的发芽因子，其释放受活动及可能的其他因素下调；（3）运动神经元撤回一些连接同时允许其他连接生长的内在倾向。
