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Published on: February 16, 2015
Cell death: a program to regenerate
Sophie Vriz1, Silke Reiter2, Brigitte Galliot2
1Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Paris, France; University Paris-Diderot, Paris, France.
Abstract:
Recent studies in Drosophila, Hydra, planarians, zebrafish, mice, indicate that cell death can open paths to regeneration in adult animals. Indeed injury can induce cell death, itself triggering regeneration following an immediate instructive mechanism, whereby the dying cells release signals that induce cellular responses over short and/or long-range distances. Cell death can also provoke a sustained derepressing response through the elimination of cells that suppress regeneration in homeostatic conditions. Whether common properties support what we name "regenerative cell death," is currently unclear. As key parameters, we review here the injury proapoptotic signals, the signals released by the dying cells, the cellular responses, and their respective timing. ROS appears as a common signal triggering cell death through MAPK and/or JNK pathway activation. But the modes of ROS production vary, from a brief pulse upon wounding, to repeated waves as observed in the zebrafish fin where ROS supports two peaks of cell death. Indeed regenerative cell death can be restricted to the injury phase, as in Hydra, Drosophila, or biphasic, immediate, and delayed, as in planarians and zebrafish. The dying cells release in a caspase-dependent manner a variety of signaling molecules, cytokines, growth factors, but also prostaglandins or ATP as recorded in Drosophila, Hydra, mice, and zebrafish, respectively. Interestingly, the ROS-producing cells often resist to cell death, implying a complex paracrine mode of signaling to launch regeneration, involving ROS-producing cells, ROS-sensing cells that release signaling molecules upon caspase activation, and effector cells that respond to these signals by proliferating, migrating, and/or differentiating.
Insights
Cell death triggers regeneration in adult animals by releasing instructive signals and eliminating suppressor cells. This "regenerative cell death" involves reactive oxygen species (ROS) and caspase-dependent signaling pathways.
Area of Science:
- Developmental Biology
- Cell Biology
- Regenerative Medicine
Background:
- Cell death is increasingly recognized as a crucial initiator of regeneration in various adult animal models, including Drosophila, Hydra, planarians, zebrafish, and mice.
- Injury-induced cell death can trigger regeneration through immediate instructive signaling or sustained derepression of regenerative pathways by eliminating suppressor cells.
- The concept of
- regenerative cell death
- suggests common underlying mechanisms, but these are not yet fully understood.
Purpose of the Study:
- To review the key parameters of regenerative cell death, including injury-induced proapoptotic signals, signals released by dying cells, cellular responses, and their temporal dynamics.
- To explore common signaling molecules and pathways involved in initiating regeneration following cell death.
- To elucidate the complex paracrine signaling networks that orchestrate regenerative responses.
Main Methods:
- Review of existing literature on cell death and regeneration across multiple model organisms.
- Analysis of signaling molecules (e.g., ROS, cytokines, growth factors, prostaglandins, ATP) and pathways (e.g., MAPK, JNK, caspase-dependent) involved in regenerative cell death.
- Examination of the temporal patterns of cell death and signaling during regeneration.
Main Results:
- Reactive oxygen species (ROS) emerge as a common signal that triggers cell death via MAPK and/or JNK pathway activation, with varying production modes (brief pulse vs. repeated waves).
- Regenerative cell death can be immediate (Hydra, Drosophila) or biphasic with delayed components (planarians, zebrafish).
- Dying cells release diverse signaling molecules, including cytokines, growth factors, prostaglandins, and ATP, in a caspase-dependent manner, often involving ROS-producing cells that resist death to signal paracrinely.
Conclusions:
- Regenerative cell death is a conserved phenomenon initiated by specific signaling events following injury.
- ROS and caspase-dependent signaling pathways play critical roles in mediating regenerative cell death and subsequent tissue repair.
- A complex paracrine signaling network involving ROS-producing, ROS-sensing, and effector cells orchestrates the initiation of regeneration.
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