Eggs never forget

part of the blame for this age-related decline belongs to lazy stem cells that sit idly by rather than repair injuries. Normally, injuries to muscle tissue activate the stem cell-like satellite cells, which then multiply and differentiate into myoblasts that can fuse with and thus repair injured muscle fibers. The injury-induced proliferation is a function of the Notch pathway. But Rando's group shows that satellite cells in older animals are unable to activate Notch and so do not repair injured muscle. Notch gets inactivated because aged muscle cells do not up-regulate Delta, the extracellular Notch ligand. In young or adult mice, Delta expression was induced by injury, and satellite cells promoted tissue repair. Repair could be prevented by blocking Notch activation. Wound repair was restored in aged mice by antibody activation of Notch. In the future, a blood-borne nonimmunogenic Delta mimic might enhance muscle regeneration in the elderly. It is unclear why or how Delta induction fails in older animals. Declining healing powers may be an evolutionary advantage, as some biologists argue that aging, by getting rid of post-reproductive individuals, is beneficial to the population as a whole. ᭿ A Muscle cell injuries (red) up-regulate Delta (green) in young mice (left), but not in old mice (right). 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 ‫ف‬ 15 proteins, including p42 MAPK, cyclin B/ Cdc2, and Cdc25. As phosphorylation is reversible but maturation is not, cells must somehow remember their hormone A Activation of the p42 pathway is irreversible unless the Mos positive feedback loop is blocked (right three lanes). 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. " ᭿ endrites are like …