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The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo.

Cell | May 17, 1996

Formation of neuromuscular synapses requires a series of inductive interactions between growing motor axons and differentiating muscle cells, culminating in the precise juxtaposition of a highly specialized nerve terminal with a complex molecular structure on the postsynaptic muscle surface. The receptors and signaling pathways mediating these inductive interactions are not known. We have generated mice with a targeted disruption of the gene encoding MuSK, a receptor tyrosine kinase selectively localized to the postsynaptic muscle surface. Neuromuscular synapses do not form in these mice, suggesting a failure in the induction of synapse formation. Together with the results of an accompanying manuscript, our findings indicate that MuSK responds to a critical nerve-derived signal (agrin), and in turn activates signaling cascades responsible for all aspects of synapse formation, including organization of the postsynaptic membrane, synapse-specific transcription, and presynaptic differentiation.

Pubmed ID: 8653786 RIS Download

Mesh terms: Agrin | Animals | Animals, Newborn | Cell Differentiation | Gene Deletion | Gene Expression | Genes, Lethal | Mice | Mice, Knockout | Muscle Fibers, Skeletal | Muscle, Skeletal | Neuromuscular Junction | Receptor Protein-Tyrosine Kinases | Receptors, Cholinergic | Signal Transduction | Synapses | Synaptic Membranes | Transcription, Genetic

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Associated grants

  • Agency: NINDS NIH HHS, Id: R01 NS036193
  • Agency: NINDS NIH HHS, Id: R01 NS036193-01A1S1
  • Agency: NINDS NIH HHS, Id: NS21579
  • Agency: NINDS NIH HHS, Id: NS27963

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