Neuromuscular development following tetrodotoxin-induced inactivity in mouse embryos.
Developmental aspects of the neuromuscular system in mouse embryos chronically paralyzed in utero with tetrodotoxin (TTX) between embryonic days 14 and 18 were studied using biochemical and histological methods. The number of lumbar spinal motoneurons (MNs) was higher in inactive embryos than in controls suggesting a decreased motoneuron cell death. In association with the increase in MN number, choline acetyltransferase activity was significantly increased in both spinal cord and peripheral synaptic sites. Paralyzed muscles exhibited a decreased number of mature myofibers and the nuclei were centrally located. Creatine kinase activity was greatly decreased and total acetylcholine receptor and receptor cluster numbers per myofiber were significantly increased in paralyzed muscles. A similar pattern of changes occurs in the neuromuscular system of the mutant mouse muscular dysgenesis (mdg). However, in contrast to the mdg mutant, tetrodotoxin-treated muscles were similar to controls in their innervation pattern, in the ultrastructural aspects of the excitation-contraction coupling system (i.e., dyads and triads) and in the extent of dihydropyridine binding. Thus, neuromuscular inactivity is not sufficient to impair the pattern of muscle innervation or the appearance of either the triadic junctions or dihydropyridine receptors. These results indicate that alterations of dihydropyridine binding sites and triads in muscular dysgenesis cannot be accounted for by inactivity but rather must reflect a more primary defect involving the structural gene(s) regulating the development of one or more aspects of muscle differentiation.
Houenou
L J
LJ
Unité de Biologie et Pathologie Neuromusculaires, INSERM U.153, Paris, France.
Pinçon-Raymond
M
M
Garcia
L
L
Harris
A J
AJ
Rieger
F
F
D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D004622:Embryo, Mammalian / Q000187:drug effects; D051379:Mice / Q000196:embryology; D008815:Mice, Inbred Strains; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D024510:Muscle Development; D009132:Muscles / Q000294:innervation; D009420:Nervous System / Q000254:growth & development*; D010243:Paralysis / Q000139:chemically induced / Q000503:physiopathology; D010275:Parasympathetic Nervous System / Q000166:cytology; D013779:Tetrodotoxin / Q000494:pharmacology*
D013779:Tetrodotoxin