During early embryogenesis, red blood cells need to be produced at a high rate to keep the embryo well oxygenated. Their precursors therefore start out growing ten times faster than the fetus as a whole. This fecundity must be shut down at the right time to prevent overgrowth. To determine how growth is limited, the group measured cell numbers at each stage of RBC development and constructed a mathematical model to fit the numerical data. The model predicted the existence of negative autoregulation as a result of physical contact between immature red cell progenitors.
Contact-initiated death is well-suited to the FAS system, in which contact between cells expressing FAS and those expressing its ligand, FASL, results in suicide in the FAS cell. With this in mind, the authors found that both FAS and FASL were expressed shortly after red blood cell maturation began, at the same time the model predicted action by the inhibitory component. When FAS/FASL-expressing cell numbers are low, they rarely interact, and death remains rare. As their numbers grow, however, their rate of interaction grows geometrically. It's then, says Socolovsky, that “the brakes come on to prevent overgrowth.”
The regulatory system not only keeps the number of cells from growing too large of its own accord, it also protects the system from external perturbations. If a trauma, for example, depletes the body of red blood cells, their new-found personal space will allow for replenishment.