During development,cell proliferation and apoptosis are orchestrated in embryos in order to ensure proper organogenesis and generation of complex multicellular tissues.In adult organisms,homeostasis in the lymphoid system and other organs and tissues is controlled by a balance between proliferation and cell death.In general,two major cell death pathways exist in mammals.One is controlled by intrinsic signals,which involves the Bcl-2 family proteins operating primarily in the mitochondria.The second so called ‘extrinsic’ pathway is initiated by type I transmembrane receptors such as Fas.In the context of apoptotic signal transduction,the death domain of FADD presumably interacts directly with the death domain of Fas and the death effector domain of FADD interacts with the death effector domain of pro-caspase-8.This leads to activation of the apical caspase-8 and subsequently downstream caspases such as caspase-3,-6 and-7.Fas-induced apoptosis is essential for maintaining lymphoid homeostasis and suppressing autoimmunity.Mutations in the Fas gene result in massive accumulation of lymphocytes of potential auto-reactivity,and lead to lymphadenopathy and autoimmune diseases in the mouse and human.