The long-term goal of this study is to enhance our understanding of the cause, prevention and cure of neuromuscular junction disorders.
The specific aim of this proposal is to test whether or not the formation of neuromuscular junction during embryonic development depends on the presence of connective tissue cells and their products in the muscle. Connective tissue cells may participate in neuromuscular synapse formation by contributing to the extracellular matrix, including the basal lamina which surrounds each muscle cell. The role of connective tissue in neuromuscular junction formation will be determined by reducing the connective tissue components of the superior oblique muscle and then monitoring the development of pre-and postsynaptic components of the neuromuscular junction. For this, the neural crest cells over the midbrain region which normally provide connective tissue cells to this muscle will be ablated in duck embryos. Ablations will be carried out before neural crest migration and development of neuromuscular junction begin. The reduction of connective tissue cells in the muscle will be verified by electron microscopy. Alterations in the basal lamina of muscle cells resulting from diminished contributions from the neural crest will be ascertained by immunohistochemical localization of its major components. The differentiation of the presynaptic components of the neuromuscular junction will be assessed by monitoring the development of synaptic vesicles and active zones in trochlear nerve terminals with electron microscopy. The differentiation of the postsynaptic components of the neuromuscular junction will be assessed by monitoring the development of acetylcholine receptors, acetylcholinesterase, junctional folds and postsynaptic density with morphological and biochemical techniques. Results of the proposed study should indicate whether or not the development of neuromuscular junction depends on interactions with connective tissue components.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD018280-07
Application #
3315301
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1983-12-01
Project End
1993-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
7
Fiscal Year
1991
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
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 (1988) Development of postsynaptic-like specializations of the neuromuscular synapse in the absence of motor nerve. Int J Dev Neurosci 6:553-65
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
Sohal, G S; Arumugam, T; Swift, T R (1986) Increased motor neuron projection during development does not increase the number of neuromuscular synapses. Exp Neurol 92:284-8
Sohal, G S; Stoney Jr, S D; Arumugam, T et al. (1986) Influence of reduced neuron pool on the magnitude of naturally occurring motor neuron death. J Comp Neurol 247:516-28
Yamashita, T; Sohal, G S (1986) Development of smooth and skeletal muscle cells in the iris of the domestic duck, chick and quail. Cell Tissue Res 244:121-31
Sohal, G S; Knox, T S; Allen Jr, J C et al. (1985) Development of the trochlear nucleus in quail and comparative study of the trochlear nucleus, nerve, and innervation of the superior oblique muscle in quail, chick, and duck. J Comp Neurol 239:227-36
Arumugam, T; Sohal, G S (1985) Myotube clusters do not bear any quantitative relation to the extent of motoneuron survival. Exp Neurol 90:281-6