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Updated: Mar 22, 2026
In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila
Published on: November 27, 2016
Different cell cycle modifications repress apoptosis at different steps independent of developmental signaling in
1Department of Biology, Indiana University, Bloomington, IN 47405.
Abstract:
Apoptotic cell death is important for the normal development of a variety of organisms. Apoptosis is also a response to DNA damage and an important barrier to oncogenesis. The apoptotic response to DNA damage is dampened in specific cell types during development. Developmental signaling pathways can repress apoptosis, and reduced cell proliferation also correlates with a lower apoptotic response. However, because developmental signaling regulates both cell proliferation and apoptosis, the relative contribution of cell division to the apoptotic response has been hard to discern in vivo. Here we use Drosophila oogenesis as an in vivo model system to determine the extent to which cell proliferation influences the apoptotic response to DNA damage. We find that different types of cell cycle modifications are sufficient to repress the apoptotic response to ionizing radiation independent of developmental signaling. The step(s) at which the apoptosis pathway was repressed depended on the type of cell cycle modification-either upstream or downstream of expression of the p53-regulated proapoptotic genes. Our findings have important implications for understanding the coordination of cell proliferation with the apoptotic response in development and disease, including cancer and the tissue-specific responses to radiation therapy.
Insights
Cell proliferation modifications can suppress the apoptotic cell death response to DNA damage, independent of developmental signals. This repression occurs at different stages, impacting cancer and radiation therapy insights.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Apoptotic cell death is crucial for organism development and acts as a barrier against cancer.
- The apoptotic response to DNA damage is often reduced during development, influenced by signaling pathways and cell proliferation.
- Disentangling the specific role of cell division in regulating apoptosis in vivo has been challenging.
Purpose of the Study:
- To investigate the influence of cell proliferation on the apoptotic response to DNA damage using Drosophila oogenesis as a model.
- To determine if cell cycle modifications can repress apoptosis independently of developmental signaling pathways.
Main Methods:
- Utilized Drosophila oogenesis as an in vivo model system.
- Induced various cell cycle modifications to assess their impact on apoptosis.
- Analyzed the apoptotic response to ionizing radiation following cell cycle alterations.
Main Results:
- Cell cycle modifications were found to be sufficient in repressing the apoptotic response to ionizing radiation.
- This repression occurred independently of developmental signaling pathways.
- The specific point of apoptosis pathway repression (upstream or downstream of p53-regulated genes) varied with the type of cell cycle modification.
Conclusions:
- Cell proliferation plays a significant role in regulating the apoptotic response to DNA damage.
- Understanding this coordination is vital for comprehending development, cancer, and tissue responses to radiation therapy.
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