The embryological development of innervation of the skeletal muscle occurs through a series of successive steps. The first step involves the projection of motor neurons to their peripheral destination. Initially, an excess number of motor neurons project to the appropriate target muscle and subsequently about one half of the motor neurons degenerate. The specific objective of this proposal is to determine whether motor neurons compete among themselves to form synaptic connections with the muscle during the course of embryonic development of innervation. The trochlear nucleus and its sole target of innervation, the superior oblique muscle of the eye, will be used to test the """"""""competition"""""""" hypothesis. Competition among neurons will be eliminated or greatly reduced by restricting the size of neuron pool initially projecting into the target muscle. The trochlear nucleus of duck embryos will be substituted with the trochlear nucleus of quails which contains fewer motor neurons through grafting of midbrain. The peripheral and central connections of the grafted trochlear motor neurons will be monitored by HRP tracing technique, histology and electron microscopy. The functional status of afferent and efferent connections of the grafted motor neurons will be assessed by electrophysiological means. Competition will be assessed by counting the number of trochlear motor neurons that survive by virtue of making appropriate synaptic connections. This proposal fits in with my long-term research objective which is to understand the basic mechanisms of mutual nerve-muscle trophic interactions and the establishment of neuromuscular synapses during the course of embryological development. The results of this study should indicate whether competition among neurons is one of the principles involved in innervation of muscles during embryogenesis. It should also increase our basic understanding of neuromuscular disorders and motor neuron abiotrophies which are clinically very common.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD017800-03
Application #
3314822
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1983-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Medical College of Georgia (MCG)
Department
Type
Schools of Medicine
DUNS #
City
Augusta
State
GA
Country
United States
Zip Code
30912
Sohal, G S (1995) Sixth Annual Stuart Reiner Memorial Lecture: embryonic development of nerve and muscle. Muscle Nerve 18:2-14
Sohal, G S (1992) The role of target size in neuronal survival. J Neurobiol 23:1124-30
Sohal, G S; Hirano, S; Kumaresan, K et al. (1992) Influence of altered afferent input on the number of trochlear motor neurons during development. J Neurobiol 23:10-6
Hirano, S; Kumaresan, K; Ali, M M et al. (1991) Synapse formation on trochlear motor neurons in relation to naturally occurring cell death during development. Int J Dev Neurosci 9:371-9
Sohal, G S; Kumaresan, K; Hirano, S et al. (1991) Synapse formation on trochlear motor neurons under conditions of increased and decreased cell death during development. Int J Dev Neurosci 9:563-70
Hirano, S; Fuse, S; Sohal, G S (1991) The effect of the floor plate on pattern and polarity in the developing central nervous system. Science 251:310-3
Sohal, G S; Stoney, S D; Campbell, L R et al. (1991) Influence of grafting a smaller target muscle on the magnitude of naturally occurring trochlear motor neuron death during development. J Comp Neurol 304:187-97
Sohal, G S; Bal, H S; Campbell, L R et al. (1990) Synapse formation on quail trochlear neurons transplanted in duck embryos before naturally occurring motor neuron death. Int J Dev Neurosci 8:9-16
Yamashita, T; Sohal, G S (1987) Embryonic origin of skeletal muscle cells in the iris of the duck and quail. Cell Tissue Res 249:31-7
Sohal, G S; Sickles, D W (1986) Embryonic differentiation of fibre types in normal, paralysed and aneural avian superior oblique muscle. J Embryol Exp Morphol 96:79-97

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