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
