3 Coordination of Cell Growth and Cell-cycle Progression in Proliferating Mammalian Cells

Abstract

The size of an animal depends mainly on the size and number of the cells it contains. Although animal growth depends on both cell growth and cell division, cell growth has, inexplicably, received much less attention than cell division. In this chapter, we consider one aspect of cell growth—how it and progression through the cell division cycle are coordinated in mammalian cells.

This coordination problem has mainly been studied in yeasts, in which cell growth appears to be rate-limiting for cell-cycle progression (Johnston et al. 1977). There is good evidence that yeasts have intracellular cell-size checkpoints, where the cell cycle can pause until cell size reaches a threshold value before progressing to the next phase of the cycle (Nurse et al. 1976; Fantes and Nurse 1977; Johnston et al. 1977; Nurse and Thuriaux 1977). In contrast, our studies on primary rat Schwann cells in culture suggest that the coordination of cell growth and cell-cycle progression in mammalian cells may be different from that in yeasts and may rely on extracellular signals rather than on intracellular controls (Conlon et al. 2001; Conlon and Raff 2003).

SCHWANN CELL GROWTH DEPENDS ON EXTRACELLULAR GROWTH FACTORS
We study Schwann cells purified from newborn rat sciatic nerve (Cheng et al. 1998). We assess cell size by removing the cells from the culture dish and measuring cell volume in a Coulter counter, and we analyze cell growth independently of cell-cycle progression by arresting the cell cycle in S phase with aphidicolin, which blocks DNA synthesis...