Activation of the p42 pathway is irreversible unless the Mos positive feedback loop is blocked (right three lanes).


Asimple positive feedback loop is a memory aid for egg cells that pushes their metabolism in one direction, based on research from Wen Xiong and James Ferrell (Stanford University, Stanford, CA). According to Ferrell, the work puts “some biochemical meat on the bones of commitment.”

That commitment occurs during egg cell maturation. Frog egg cells mature from a paused G2-like state in response to a hormone stimulus. Even a transient stimulus pushes cells through maturation to meiosis II via a kinase/phosphatase cascade of ∼15 proteins, including p42 MAPK, cyclin B/Cdc2, and Cdc25. As phosphorylation is reversible but maturation is not, cells must somehow remember their hormone encounter. The authors now show that this memory lies in a positive feedback loop in the p42 pathway.

Feedback is provided by the protein Mos, which activates p42, which in turn promotes Mos accumulation. By blocking the effects of Mos, the authors show that p42 MAPK activation becomes reversible in the absence of positive feedback. The simplicity of positive feedback loops explains why researchers stumble upon them so often, according to Ferrell, who hopes “clever systems biologists will uncover other examples [of] irreversible cell fates established by positive feedback loops.” ▪


Xiong, W., and J.E. Ferrell.