MAMMALIAN MYOGENESIS SUBSEQUENT TO FETAL DENERVATION

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In vivo myogenesis occurs simultaneously with the development and maturation of the fetal nervous system. Because the mammalian fetus has not been easily manipulated, much of what we know about nerve-muscle relationships during development has been gained from studies of developing chick. Recent studies suggest that nerve-muscle relationships in mammalian fetuses may differ from those in chick. A new technique which permits laser ablation of the lumbosacral region of the fetal, murine spinal cord, without interfering with fetal viability and further maturation, will allow us to determine the effect of fetal denervation on myotube formation, myotube survival and on the generation of myotube diversity in mammalian muscles. Evaluations will be made with electron microscopy, quantitative morphometry, gel electrophoresis and immunocytochemistry. These studies will provide information concerning alterations in genetically determined patterns of myogenesis by an environmental factor (i.e., the developing motoneuron). Little is known about the effects of axotomy, performed at various fetal stages, on the survival of mammalian motoneurons. Techniques which permit transection of the ventral roots of spinal nerves or of the sciatic nerve will allow determination of whether mammalian axons can survive axotomy and whether (and under what conditions) they can innervate striated muscle. If axotomized motoneurons survive, the effect of delayed innervation and/or transient fetal denervation on muscle development will be assessed. If they fail to survive, alterations in the size and location of motoneuron pools to adult muscles subjected to partial denervation during fetal development will be determined. Evaluations will be made with electron microscopy, physiology and by examining the spinal cords of mice whose muscles were injected with HRP. The proposed studies are relevant to human development.