control is how total cell mass is determined. Developmental Neurobiology Programme Both local and systemic controls determine organ Medical Research Council Laboratory for Molecular size, but their relative importance can vary greatly. If Cell Biology multiple fetal thymus glands are transplanted into a de-University College London veloping mouse, each grows to its normal adult size, London WC1E 6BT suggesting that their growth is mainly controlled by fac-United Kingdom tors within the thymus (Metcalf, 1963). If the same experiment is performed with fetal spleens, the total mass of the transplanted spleens attains the mass of one normal "The most obvious differences between different aniadult spleen, suggesting that their growth is mainly conmals are differences in size, but for some reason the trolled by factors outside the spleen (Metcalf, 1964). zoologists have paid singularly little attention to them." Similar transplantation experiments, as well as tissue -J. B. S. Haldane, On Being the Right Size, 1927 culture experiments, indicate that most animal organs grow to a characteristic size under autonomous controls (Goss, 1978; Bryant and Simpson, 1984). Systemic fac-Some proclaim that the major principles of development tors such as hormones, however, influence final organ are now understood (Wolpert, 1996). Yet one of the most size. Growth hormone (GH), for instance, which the pitufundamental aspects of development remains as mysteitary gland secretes under the control of the hypothalarious as ever-how the size of an animal or plant is mus, plays a major part in stimulating postnatal mammadetermined. How is it, for example, that we grow to be lian growth: children deficient in GH become dwarfs, larger than mice and our arms grow to be the same whereas those with excessive GH become giants. GH length? Although it is clear that genes play the predomistimulates growth largely by inducing the liver and other nant part in determining size, it is largely unknown how organs to produce insulin-like growth factor 1 (IGF1) they do so. Considering the importance of size control, (Heyner and Garside, 1994, and see below). it is remarkable that so little attention has been paidAlthough genes largely determine the size of an animal to it.or organ, environmental factors such as nutrition or The size of an animal, organ, or appendage depends functional load also play a part. During development, on the number and size of the cells it contains as well for example, both animals deprived of adequate nourishas on the amount of extracellular matrix and fluid. We ment and muscles deprived of tension end up smaller shall ignore these extracellular components in this rethan normal. view and consider only the controls that regulate cell Differences in size between animals of the same or size and cell numbers, as it is mainly these that deterdifferent species can reflect differences in cell size, cell mine animal size. We begin by listing some basic obsernumber, or both. Cell numbers depend on both cell divivations on size control in an...

Both cell growth (cell mass increase) and progression through the cell division cycle are required for sustained cell proliferation. Proliferating cells in culture tend to double in mass before each division, but it is not known how growth and division rates are co-ordinated to ensure that cell size is maintained. The prevailing view is that coordination is achieved because cell growth is rate-limiting for cell-cycle progression. 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 cells. 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.