Motor neurone and muscle nuclear changes in development and disease
The primary gene defects of hereditary neuromuscular disorders have not, as yet, been determined. Research has contributed much to our understanding of many aspects of these diseases, but since this has been directed towards the secondary phenomena, the exact role of the nucleus in the pathogenesis of these genetic disorders remains unclear. It was felt that a study of the motor neurone and muscle nucleus in development and disease might reveal the extent of its participation in some of these disease processes. 1. A quantitative histochemical and histometric study of the developing anterior horn cell nucleus during fetal life was undertaken. The result suggested that the 12th to 14th week period is critical for the differentiation of the spinal motor neurone. 2. In contrast to this, a similar study of the deve¬ loping muscle cell nuclei revealed no major changes in muscle nuclear size or composition. During normal post-natal muscle growth an increase in the number of nuclei per muscle fibre seems to be responsible for the maintenance of a constant nucleo-cytoplasmic ratio. 3. The nuclear size of multinucleated myoblasts arising from both normal and dystrophic muscle in tissue culture was measured. Myoblasts from dystrophic muscle exhibited larger nuclei than those from normal muscle. 4. An increase in muscle nuclear size was also detected in a number of muscle samples from male fetuses at risk for Duchenne muscular dystrophy. Both of these findings suggest possible changes in the nucleo-cytoplasmic relationship. 5. In an attempt to elucidate the extent of the parti¬ cipation of the muscle nucleus in the pathogenic process of a number of characteristic neuromuscular disorders, the nuclear size and/or the number of nuclei per cross-sectioned muscle fibre, were estimated. An increased nuclear size was observed in Duchenne muscular dystrophy and an increase in the number of nuclei was detected in chronic neurogenic atrophies, in diabetic neuropathy and in myotonic dystrophy. Such a finding would seem to indicate a fundamental difference in the response of the muscle fibre nucleus to the neurogenic and myopathic processes. 6. In addition, the growth of the human cervical vertebral canal and spinal cord during normal fetal development was studied. The results suggested that these two parts of the developing body exhibit the same developmental pattern. The rate of this parallel growth is lower than that of the body as a whole, but similar to that reported for the brain. In conclusion, although the techniques used did not reveal a direct relationship in the developmental pattern of anterior horn cell nuclei and myonuclei, they did provide normal values for comparison with data obtained from diseased neural and muscle tissue. The finding that in Duchenne muscular dystrophy (from tissue culture, fetuses at risk and juvenile biopsies) the muscle nuclei are enlarged, points to an underlying difference from various neuropathies in which the nuclei are increased in number.