Abstract
Apoptotic cells can produce signals to instruct cells in their local environment, including ones that stimulate engulfment and proliferation. We identified a novel mode of communication by which apoptotic cells induce additional apoptosis in the same tissue. Strong induction of apoptosis in one compartment of the Drosophila wing disc causes apoptosis of cells in the other compartment, indicating that dying cells can release long-range death factors. We identified Eiger, the Drosophila tumor necrosis factor (TNF) homolog, as the signal responsible for apoptosis-induced apoptosis (AiA). Eiger is produced in apoptotic cells and, through activation of the c-Jun N-terminal kinase (JNK) pathway, is able to propagate the initial apoptotic stimulus. We also show that during coordinated cell death of hair follicle cells in mice, TNF-α is expressed in apoptotic cells and is required for normal cell death. AiA provides a mechanism to explain cohort behavior of dying cells that is seen both in normal development and under pathological conditions. DOI:http://dx.doi.org/10.7554/eLife.01004.001.
Highlights
Apoptosis is a distinct form of programmed cell death in which cells activate an intrinsic suicide program to self-destruct
Apoptotic cells are normally very rapidly cleared in living tissues, undead cells persist for long times and thereby permit analysis of signaling events associated with the induction of apoptosis
We typically saw two large clusters of dying cells in the wing pouch. It appears that cells in this region of the wing disc are more susceptible to apoptosis, as indicated by the fact that higher rates of cell death within this region were observed after X-irradiation and hid over-expression (Milan et al, 1997; Moon et al, 2005)
Summary
Apoptosis is a distinct form of programmed cell death in which cells activate an intrinsic suicide program to self-destruct. Mitogenic signaling by apoptotic cells has been reported for a diversity of animals, from Hydra, to flat worms, Drosophila and vertebrates, and it has been implicated in regeneration, wound healing and tumor growth (Tseng et al, 2007; Chera et al, 2009; Bergmann and Steller, 2010; Li et al, 2010; Pellettieri et al, 2010; Huang et al, 2011). This mechanism appears well suited to communicate cellular loss to stem and progenitor cells in the tissue environment to stimulate proliferation and tissue repair.
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