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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
3R01HD025630-03S1
Application #
3326827
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1990-03-01
Project End
1994-02-28
Budget Start
1993-05-01
Budget End
1994-02-28
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
D'Onofrio, Brian M; Turkheimer, Eric N; Eaves, Lindon J et al. (2003) The role of the children of twins design in elucidating causal relations between parent characteristics and child outcomes. J Child Psychol Psychiatry 44:1130-44
Washabaugh, C H; Ontell, M P; Kant, J A et al. (2001) Effect of chronic denervation and denervation-reinnervation on cytoplasmic creatine kinase transcript accumulation. J Neurobiol 47:194-206
Washabaugh, C H; Ontell, M P; Kant, J A et al. (1999) Creatine kinase transcript accumulation: effect of nerve during muscle development. Dev Dyn 215:285-96
Washabaugh, C H; Ontell, M P; Shan, Z et al. (1998) Role of the nerve in determining fetal skeletal muscle phenotype. Dev Dyn 211:177-90
Ontell, M; Ontell, M P; Buckingham, M (1995) Muscle-specific gene expression during myogenesis in the mouse. Microsc Res Tech 30:354-65
Ontell, M; Ontell, M P; Sopper, M M et al. (1993) Contractile protein gene expression in primary myotubes of embryonic mouse hindlimb muscles. Development 117:1435-44
Ontell, M P; Sopper, M M; Lyons, G et al. (1993) Modulation of contractile protein gene expression in fetal murine crural muscles: emergence of muscle diversity. Dev Dyn 198:203-13
Hughes, D S; Schade, R R; Ontell, M (1992) Ablation of the fetal mouse spinal cord: the effect on soleus muscle cytoarchitecture. Dev Dyn 193:164-74
Hughes, D S; Ontell, M (1992) Morphometric analysis of the developing, murine aneural soleus muscle. Dev Dyn 193:175-84
LaFramboise, W A; Daood, M J; Guthrie, R D et al. (1991) Emergence of the mature myosin phenotype in the rat diaphragm muscle. Dev Biol 144:1-15

Showing the most recent 10 out of 11 publications