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

Cell. 1996 May 17;85(4):501-12. doi: 10.1016/s0092-8674(00)81251-9.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Agrin / physiology
  • Animals
  • Animals, Newborn
  • Cell Differentiation / genetics
  • Gene Deletion
  • Gene Expression / physiology
  • Genes, Lethal / physiology
  • Mice
  • Mice, Knockout
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / ultrastructure
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / embryology
  • Muscle, Skeletal / innervation
  • Neuromuscular Junction / chemistry*
  • Neuromuscular Junction / embryology
  • Neuromuscular Junction / physiology
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptors, Cholinergic / genetics
  • Signal Transduction / physiology
  • Synapses / chemistry
  • Synapses / physiology
  • Synaptic Membranes / physiology
  • Transcription, Genetic / physiology


  • Agrin
  • Receptors, Cholinergic
  • MUSK protein, human
  • Receptor Protein-Tyrosine Kinases