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GENETIC ORIGIN. "The identification of a regulated cell death program inducing an apoptotic phenotype in nine different single-celled eukaryote organisms that belong to four diverging branches of the eukaryote phylogenic tree provides a paradigm for a widespread role for programmed cell death in the control of cell survival, and raises the question of the origin and nature of the genes that may be involved in the execution and regulation of such a process." http://www.nature.com/cdd/journal/v9/n4/full/4400950a.html View in LinkedIn

TRIGGERS. "Programmed cell death induction may depend essentially on cell-lineage information, such as in the nematode Caenorhabditis elegans, on the activation of gene transcription, such as in the fruitfly Drosophila melanogaster, or, in a more stochastic way, on a combination of cell-lineage information, intercellular signaling, transcription factor activation and cytoplasmic second messengers, such as in mammals." http://www.nature.com/cdd/journal/v9/n4/full/4400950a.html View in LinkedIn

WIDE AND OLD. "Various forms of regulated programmed cell death have now been described in nine species of unicellular eukaryotes, belonging to four different branches whose phylogenic divergence is believed to range from around two to one billion years ago." http://www.nature.com/cdd/journal/v9/n4/full/4400950a.html View in LinkedIn

EXTERNAL SIGNALS. "In all cases that have been studied to date, programmed cell death is regulated by signals provided by other cells, either in the form of cell-lineage information, of soluble mediators, or of cell-to-cell contacts." http://www.nature.com/cdd/journal/v9/n4/full/4400950a.html View in LinkedIn

SINGLE OR MULTIPLE? "Did this frontier arise after the initial three billion years of evolution of single-celled organisms, at the time at which the first multicellular organisms emerged, or did this frontier arise in the kingdom of the single-celled organism, prior to the emergence of multicellular organisms?" http://www.nature.com/cdd/journal/v9/n4/full/4400950a.html View in LinkedIn

CONSERVED. "Programmed cell death has been found to operate in all multicellular animals studied so far, including cnidaria, nematodes, insects, amphibians, birds and mammals. The evolutionary conservation of programmed cell death in the animal kingdom does not only involve its existence and role, but extends to some central aspects of its genetic control, and to important aspects of its most frequent phenotype, apoptosis." http://www.nature.com/cdd/journal/v9/n4/full/4400950a.html View in LinkedIn

THE TRANSITION POINT. "In other words, was there a period 'before' programmed cell death, in which cells died only 'from without', as a result of chance and environmental destruction, and a period 'after' programmed cell death, in which regulated self-destruction, the capacity to trigger premature death 'from within', became one of the intrinsic properties of the cells?" http://www.nature.com/cdd/journal/v9/n4/full/4400950a.html View in LinkedIn

DEATH FOR ADULT HOMEOSTASIS. "Programmed cell death is also crucial in the adult, by allowing tissue homeostasis, elimination of damaged or abnormal cells, and defense against infections. It may also play an important but poorly explored physiological role in metabolism, by allowing energy recycling through the ingestion of dying cells by neighboring cells." http://www.nature.com/cdd/journal/v9/n4/full/4400950a.html View in LinkedIn

FIRST DEATH GENES. "Accordingly, if one believes that programmed cell death is an ubiquitous, highly conserved, and essential feature of most, or all, multicellular organisms, the question of the evolutionary origin of programmed cell death may benefit from being asked in the following way: when and how were genes first selected, that allowed the regulation of programmed cell death?" http://www.nature.com/cdd/journal/v9/n4/full/4400950a.html View in LinkedIn

SELECTION OF DEATH GENES. "Any mutant gene that might have emerged randomly and allowed regulated cell suicide, would have rapidly and obligatorily led to the counter-selection of the individual cell expressing such a mutant gene." http://www.nature.com/cdd/journal/v9/n4/full/4400950a.html View in LinkedIn