神经肌肉接头是研究突触形成的经典模型，但其形成的机制仍不完全清楚。乙酰胆碱受体聚集是神经肌肉接头形成的关键步骤和标志。我们发现Wnt信号能在肌肉细胞中诱导乙酰胆碱受体聚集。降低Wnt受体Ror的表达可以抑制受体聚集，降低在神经肌肉接头形成中有关键作用的蛋白MuSK的活性。这些结果表明Wnt/Ror信号调控乙酰胆碱受体的聚集，提示其在神经肌肉接头形成中发挥作用。本研究将从分子及细胞水平阐明在调控乙酰胆碱受体聚集的过程中，Wnt与Ror结合的分子机制，以及Wnt/Ror信号与agrin/LRP4/MuSK信号的相互影响，并应用靶基因技术手段阐明Wnt/Ror信号对小鼠神经肌肉接头形成的调控作用，揭示非神经支配的神经肌肉接头早期发育对受神经支配的突触形成的影响。本研究有助于理解突触形成的分子机理，为相关疾病的诊断和治疗提供理论依据。

The neuromuscular junction is the classical model to study synapse formation, but the molecular mechanism of the neuromuscular junction formation remains unclear. Acetylcholine receptor (AChR) clustering is the critical step and hallmark event for the neuromuscular junction formation. We found that Wnt induced AChR clustering in muscle cells. Reducing protein level of Wnt receptor Ror inhibited AChR clustering, and MuSK, one essential protein for the neuromuscular junction formation, phosphorylation and activity. These observations suggest that Wnt/Ror signal could regulate AChR clustering and the neuromuscular junction formation. Here we propose to characterize the interaction between Wnt and Ror, and the crosstalk between Wnt/Ror signal and agrin/LRP4/MuSK signal. We also determine to study the in vivo function of Wnt/Ror signal during the neuromuscular junction formation by use of transgenic mice, and reveal the importance of prepatterning in the muscle for neural synapse formation. Our study will shed light on understanding the molecular mechanism of synapse formation, and help to develop novel diagnostic and therapeutic approaches for related neurological diseases.