Michael C. O'Neill

Growth and differentiation during myogenesis in the chick embryo.

A general method for describing the complex dynamics of cell populations over an extended period of growth and differentiation in a developing tissue is presented. The measurements required to produce a unique description are defined. Skeletal muscle development in the thigh and breast of the chick embryo is analyzed, using this method, during the period of embryonic development between Day 7 and Day 17. A unique quantitation of growth and differentiation for the period from Day 11 to Day 17 is developed. The pectoralis major is compared with the averaged behavior of the thigh musculature. In each case, a single partitioning rule holds for more than 10 generations during the main myogenic period. In the pectoralis, approximately 51% of the cells entering G1 in each generation continue in the cell cycle; in the thigh, which experiences substantially greater overall growth, approximately 58% of the cells entering G1 in each generation continue in the cell cycle. No significant cell death is detected. Thus, in each case, the absolute number of myoblasts is increasing while the fractional value of myoblasts in the population is decreasing over a fivefold range. These results are discussed in terms of several quantitative models for the possible basis of the observed population dynamics.

Male gonadotrophic factor in brain and blood of photoperiodically stimulated slugs

A pulmonate male gonadotrophic factor (MGF) has been described that is released from cerebral ganglia of male-phase slugs (Limax maximus). This factor produces, directly or indirectly, an increase in spermatogonial proliferation as determined by in vivo incorporation of [3H]thymidine into gonadal DNA. In the present investigation MGF activity was demonstrated in saline homogenates of male-phase cerebral ganglia by injecting homogenates into immature slugs for 5 consecutive days and assaying gonadal [3H]thymidine incorporation on Day 7. Dose-response data indicate that daily administration of as little as 0.1 brain equivalent can produce a significant stimulation in incorporation. Comparison of brain homogenates from immature (short-day) and male-phase (long-day) animals has shown that male-phase cerebral ganglia contain substantially more MGF activity than immature ganglia. Similar injection experiments using slug blood plasma showed that activity is present in male-phase blood but not in the blood of short-day immatures. MGF activity in long-day brain homogenates and blood plasma was found to be associated with a molecular weight fraction of 50 to 100 kDa obtained by ultrafiltration. Activity could be reduced or destroyed by treatment with trypsin or by heating. The present findings suggest that MGF is a proteinaceous factor of substantial size. It appears that both the synthesis and the secretion of MFG are stimulated in slugs that are in their male developmental phase as a result of prior exposure to long-day photoperiods.

Population modeling in muscle cell culture: Comparisons with experiments

Abstract A specific model is developed for the kinetics of fusion which provides a temporal description of the myoblast and myotube populations. The predictions of the model are compared with experimental results on the rate of DNA accumulation, the rate of thymidine incorporation, and the relationship between fusion and data in the literature for several parameters: the rate of decline in cytoplasmic DNA polymerase activity, the cellular distribution of AChE activity, and the initiation of myosin synthesis.