High GGF (top) shrinks cells relative to low GGF (bottom).


How does a growing cell know that it's big enough to divide? Challenging a long-held view, a new study argues that the decision depends mainly on external factors that stimulate growth and division rather than an internal mechanism for assessing size.

The standard take on the relationship between growth and division envisions a “size checkpoint” during the cell cycle, where the cell somehow gauges its girth before advancing further. However, Ian Conlon (University College London, England) and colleagues found that they could separate growth from progression through the cell cycle by manipulating the concentrations of insulin-like growth factor-1 (IGF-1) and glial growth factor (GGF). Of the two, only IGF-1 incited growth in rat Schwann cells, while GGF drove cell cycle progression without speeding growth. Applying that discovery, the researchers used GGF to accelerate the cell cycle and gradually shrink cultured cells. The cells grown in high GGF concentrations were ∼20 percent smaller than cells grown in low GGF.

According to Conlon, the findings demonstrate that the decision to divide doesn't hinge on reaching a set size. Instead, the relative concentrations of several growth factors and mitogens probably provide the crucial cues, and as a result cell size is variable. However, he cautions, the results don't discount the influence of size. “It's resonably clear that growth does have an effect on cell cycle progression, but it's usually not the limiting factor,” he says.

Mutations can alter cell size at division, but this is the first study to show that manipulating external factors has the same effect, says developmental biologist Thomas Neufeld of the University of Minnesota in Minneapolis. Now, we need to determine how widespread this mechanism is, he says. ▪


Conlon, I.J., et al.
Nat. Cell Biol