title: The receptor tyrosine kinase MuSK is required for neuromuscular junction formation in vivo.
abstract: 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.
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: DeChiara
authors.forename: David C
authors.initials: DC
authors.lastname: Bowen
authors.forename: David M
authors.initials: DM
authors.lastname: Valenzuela
authors.forename: Mary V
authors.initials: MV
authors.lastname: Simmons
authors.forename: William T
authors.initials: WT
authors.lastname: Poueymirou
authors.forename: Susan
authors.initials: S
authors.lastname: Thomas
authors.forename: Erika
authors.initials: E
authors.lastname: Kinetz
authors.forename: Debra L
authors.initials: DL
authors.lastname: Compton
authors.forename: Eduardo
authors.initials: E
authors.lastname: Rojas
authors.forename: John S
authors.initials: JS
authors.lastname: Park
authors.forename: Cynthia
authors.initials: C
authors.lastname: Smith
authors.forename: Peter S
authors.initials: PS
authors.lastname: DiStefano
authors.forename: David J
authors.initials: DJ
authors.lastname: Glass
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Burden
authors.forename: George D
authors.initials: GD
authors.lastname: Yancopoulos
mesh_terms: D018171:Agrin / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000235:genetics; D017353:Gene Deletion; D015870:Gene Expression / Q000502:physiology; D005804:Genes, Lethal / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000737:chemistry / Q000196:embryology / Q000294:innervation; D009469:Neuromuscular Junction / Q000737:chemistry* / Q000196:embryology / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000502:physiology*; D011950:Receptors, Cholinergic / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000737:chemistry / Q000502:physiology; D013570:Synaptic Membranes / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D018171:Agrin; D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases