title: An explant muscle model to examine the refinement of the synaptic landscape.
abstract: Signals from nerve and muscle regulate the formation of synapses. Transgenic mouse models and muscle cell cultures have elucidated the molecular mechanisms required for aggregation and stabilization of synaptic structures. However, far less is known about the molecular pathways involved in redistribution of muscle synaptic components. Here we established a physiologically viable whole-muscle embryonic explant system, in the presence or absence of the nerve, which demonstrates the synaptic landscape is dynamic and malleable. Manipulations of factors intrinsic to the muscle or extrinsically provided by the nerve illustrate vital functions during formation, redistribution and elimination of acetylcholine receptor (AChR) clusters. In particular, RyR1 activity is an important mediator of these functions. This physiologically relevant and readily accessible explant system provides a new approach to genetically uncouple nerve-derived signals and for manipulation via signaling molecules, drugs, and electrical stimulation to examine early formation of the neuromuscular circuit.
authors.affiliation: Howard Hughes Medical Institute, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO 80045, United States. Electronic address: martin.hanson@ucdenver.edu.
authors.forename: Martin Gartz
authors.initials: MG
authors.lastname: Hanson
authors.affiliation: Howard Hughes Medical Institute, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO 80045, United States.
authors.forename: Lee A
authors.initials: LA
authors.lastname: Niswander
mesh_terms: D000818:Animals; D003964:Diaphragm / Q000196:embryology* / Q000502:physiology*; D004558:Electric Stimulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008822:Mice, Transgenic; D010791:Phrenic Nerve / Q000196:embryology / Q000502:physiology; D011950:Receptors, Cholinergic / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D046509:Tissue Culture Techniques / Q000379:methods; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D060509:Wnt3A Protein / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D011950:Receptors, Cholinergic; D019837:Ryanodine Receptor Calcium Release Channel; D014157:Transcription Factors; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; C000592747:ryanodine receptor 1, mouse; C084059:Hb9 protein, mouse
keywords: Acetylcholine receptor; Agrin; Muscle fiber; Neuregulin; Neuromuscular junction; Synapse formation