摘要:SummaryActivity-dependent calcium signals in developing muscle play a crucial role in neuromuscular junction (NMJ) formation. However, its downstream effectors and interactions with other regulators of pre- and postsynaptic differentiation are poorly understood. Here, we demonstrate that the skeletal muscle calcium channel CaV1.1 and β-catenin interact in various ways to control NMJ development. They differentially regulate nerve branching and presynaptic innervation patterns during the initial phase of NMJ formation. Conversely, they cooperate in regulating postsynaptic AChR clustering, synapse formation, and the proper organization of muscle fibers in mouse diaphragm. CaV1.1 does not directly regulate β-catenin expression but differentially controls the activity of its transcriptional co-regulators TCF/Lef and YAP. These findings suggest a crosstalk between CaV1.1 and β-catenin in the activity-dependent transcriptional regulation of genes involved in specific pre- and postsynaptic aspects of NMJ formation.Graphical abstractDisplay OmittedHighlights•Neuromuscular junction formation requires either muscle calcium or β-catenin signaling•Complementary actions of CaV1.1 and β-catenin control presynaptic innervation patterns•Parallel actions of CaV1.1 and β-catenin are crucial for postsynaptic AChR clustering•Loss of CaV1.1 differentially regulates activity of β-catenin targets TCF/Lef and YAPBiological sciences; Developmental neuroscience; Cell biology; Developmental biology