Abstract
Both cell growth (cell mass increase) and progression through the cell division cycle are required for sustained cell proliferation1. Proliferating cells in culture tend to double in mass before each division2, but it is not known how growth and division rates are co-ordinated to ensure that cell size is maintained1,3,4,5. The prevailing view is that coordination is achieved because cell growth is rate-limiting for cell-cycle progression6,7,8,9,10. Here, we challenge this view. We have investigated the relationship between cell growth and cell-cycle progression in purified rat Schwann cells, using two extracellular signal proteins that are known to influence these cells11,12,13. We find that glial growth factor (GGF) can stimulate cell-cycle progression without promoting cell growth. We have used this restricted action of GGF to show that, for cultured Schwann cells, cell growth rate alone does not determine the rate of cell-cycle progression and that cell size at division is variable and depends on the concentrations of extracellular signal proteins that stimulate cell-cycle progression, cell growth, or both.
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Acknowledgements
We thank M. Marchionni for the recombinant GGF 2, L. Cheng for her expert help, A. Lloyd, S. Leevers, D. Knight, P. Nurse, R. Brooks and the Raff and Lloyd labs for helpful discussions, and the Medical Research Council for support.
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Figure S1 IGF-I but not GGF promotes the growth of quiescent cells in the presence of aphidicolin. (PDF 33 kb)
Figure S2 Cells in IGF-I (100 ng ml -1 ), forskolin and aphidicolin grow at the same rate in high (20 ng ml -1 ) or low (2 ng ml -1 ) GGF.
Figure S3 Cells proliferating in IGF-I, GGF and forskolin become progressively smaller
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Conlon, I., Dunn, G., Mudge, A. et al. Extracellular control of cell size. Nat Cell Biol 3, 918–921 (2001). https://doi.org/10.1038/ncb1001-918
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DOI: https://doi.org/10.1038/ncb1001-918
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