Death in the balance.

Abstract

Two major hypotheses concerning programmed cell death are that it is the end result of a gene expression pathway and that it is the cellular response to conflicting growth control signals. These ideas are examined, and their potential applicant to neuronal cell death during development is discussed. Since most mammalian genes involved in cell death have other functions, it is possible that a novel set of death genes does not exist in mammals. Instead, the genes identified may serve to link an initial stimulus to die with the cellular events that actually cause death, primarily by providing regulatory signals that direct the decision. The idea of cell death as a response to conflicting growth regulatory signals, initially derived from studies on cycling, non-neuronal cells, is applied to proliferating neuronal precursors and postmitotic neurons. How neuronal death during development might be the outcome of conflicting signals, and how retinoblastoma protein might negotiate "death by conflict" in different populations of neurons is discussed.