The neuromuscular junction (NMJ) is a unique, specialized chemical synapse that plays a crucial role in transmitting and amplifying information from spinal motor neurons to skeletal muscles. NMJ complexity ensures closely intertwined interactions between numerous synaptic vesicles, signaling molecules, ion channels, motor neurons, glia, and muscle fibers, making it difficult to dissect the underlying mechanisms and factors affecting neurodegeneration and muscle loss. Muscle fiber or motor neuron cell death followed by rapid axonal degeneration due to injury or disease has a debilitating effect on movement and behavior, which adversely affects the quality of life. It thus becomes imperative to study the synapse and intercellular signaling processes that regulate plasticity at the NMJ and elucidate mechanisms and pathways at the cellular level. Studies using in vitro 2D cell cultures have allowed us to gain a fundamental understanding of how the NMJ functions. However, they do not provide information on the intricate signaling networks that exist between NMJs and the biological environment. The advent of 3D cell cultures and microfluidic lab-on-a-chip technologies has opened whole new avenues to explore the NMJ. In this perspective, we look at the challenges involved in building a functional NMJ and the progress made in generating models for studying the NMJ, highlighting the current and future applications of these models.

中文翻译：

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迈向建立神经肌肉交界处：研究突触发生和神经退行性变的体外模型。

神经肌肉接头（NMJ）是独特的，专门的化学突触，在从脊髓运动神经元到骨骼肌的传递和放大信息中起着至关重要的作用。NMJ的复杂性可确保许多突触小泡，信号分子，离子通道，运动神经元，神经胶质和肌肉纤维之间紧密交织的相互作用，从而难以剖析影响神经退行性和肌肉丧失的潜在机制和因素。肌肉纤维或运动神经元细胞死亡，然后由于伤害或疾病而导致轴突迅速变性，会对运动和行为产生衰弱作用，对生活质量产生不利影响。因此，有必要研究突触和细胞间信号传导过程，这些过程调节NMJ的可塑性并阐明细胞水平的机制和途径。使用体外2D细胞培养的研究使我们对NMJ的功能有了基本的了解。但是，它们不提供有关NMJ与生物环境之间存在的复杂信号网络的信息。3D细胞培养和微流体芯片实验室技术的出现为探索NMJ开辟了全新的途径。从这个角度来看，我们着眼于构建功能性NMJ所面临的挑战以及在生成用于研究NMJ的模型方面所取得的进展，重点介绍了这些模型的当前和未来应用。3D细胞培养和微流体芯片实验室技术的出现为探索NMJ开辟了全新的途径。从这个角度来看，我们着眼于构建功能性NMJ所面临的挑战以及在生成用于研究NMJ的模型方面所取得的进展，重点介绍了这些模型的当前和未来应用。3D细胞培养和微流体芯片实验室技术的出现为探索NMJ开辟了全新的途径。从这个角度来看，我们着眼于构建功能性NMJ所面临的挑战以及在生成用于研究NMJ的模型方面所取得的进展，重点介绍了这些模型的当前和未来应用。