The Receptor Tyrosine Kinase MuSK Is Required for Neuromuscular Junction Formation In Vivo

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 rec...

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Bibliographic Details
Published in:Cell 1996-05, Vol.85 (4), p.501-512
Main Authors: DeChiara, Thomas M, Bowen, David C, Valenzuela, David M, Simmons, Mary V, Poueymirou, William T, Thomas, Susan, Kinetz, Erika, Compton, Debra L, Rojas, Eduardo, Park, John S, Smith, Cynthia, DiStefano, Peter S, Glass, David J, Burden, Steven J, Yancopoulos, George D
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(00)81251-9