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Updated: Aug 21, 2026
Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Apoptotic cells can induce compensatory cell proliferation through the JNK and the Wingless signaling pathways
Hyung Don Ryoo1, Travis Gorenc, Hermann Steller
1Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, Box 252, New York, NY 10021, USA.
Abstract:
In many metazoans, damaged and potentially dangerous cells are rapidly eliminated by apoptosis. In Drosophila, this is often compensated for by extraproliferation of neighboring cells, which allows the organism to tolerate considerable cell death without compromising development and body size. Despite its importance, the mechanistic basis of such compensatory proliferation remains poorly understood. Here, we show that apoptotic cells express the secretory factors wingless (wg) and decapentaplegic (dpp). When cells undergoing apoptosis were kept alive with the caspase inhibitor p35, excessive nonautonomous cell proliferation was observed. Significantly, wg signaling is necessary and, at least in some cells, also sufficient for mitogenesis under these conditions. Finally, we provide evidence that the DIAP1 antagonists reaper and hid can activate the JNK pathway and that this pathway is required for inducing wg and cell proliferation. These findings support a model where apoptotic cells activate signaling cascades for compensatory proliferation.
Insights
Compensatory cell proliferation in Drosophila is triggered by apoptotic cells releasing signaling factors. This process, crucial for development, involves wingless (wg) signaling and the JNK pathway.
Area of Science:
- Developmental biology
- Cellular biology
- Signaling pathways
Background:
- Metazoans eliminate damaged cells via apoptosis.
- Drosophila melanogaster compensates for cell death through compensatory proliferation, maintaining development and body size.
- The mechanisms underlying compensatory proliferation are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms driving compensatory proliferation in Drosophila.
- To identify the signaling pathways and factors involved in this process.
Main Methods:
- Utilized the caspase inhibitor p35 to maintain apoptotic cells.
- Investigated the role of wingless (wg) and decapentaplegic (dpp) signaling.
- Examined the involvement of the JNK pathway and DIAP1 antagonists (reaper, hid).
Main Results:
- Apoptotic cells were found to express wingless (wg) and decapentaplegic (dpp).
- Inhibition of apoptosis led to excessive nonautonomous cell proliferation.
- Wingless (wg) signaling was both necessary and sufficient for mitogenesis.
- DIAP1 antagonists activated the JNK pathway, which is required for inducing wg and proliferation.
Conclusions:
- Apoptotic cells initiate signaling cascades that promote compensatory proliferation.
- Wingless (wg) and JNK pathways are key mediators of this response in Drosophila.
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