A steroid-controlled global switch in sensitivity to apoptosis during Drosophila development
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Updated: May 4, 2026
In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila
Published on: November 27, 2016
Yunsik Kang1, Arash Bashirullah1
1Division of Pharmaceutical Sciences, University of Wisconsin, 777 Highland Avenue, Madison, WI 53705-2222, USA; Laboratory of Genetics Graduate Program, University of Wisconsin-Madison, Madison, WI, USA.
Abstract:
Precise control over activation of the apoptotic machinery is critical for development, tissue homeostasis and disease. In Drosophila, the decision to trigger apoptosis--whether in response to developmental cues or to DNA damage--converges on transcription of inhibitor of apoptosis protein (IAP) antagonists reaper, hid and grim. Here we describe a parallel process that regulates the sensitivity to, rather than the execution of, apoptosis. This process establishes developmental windows that are permissive or restrictive for triggering apoptosis, where the status of cells determines their capacity to die. We characterize one switch in the sensitivity to apoptotic triggers, from restrictive to permissive, that occurs during third-instar larval (L3) development. Early L3 animals are highly resistant to induction of apoptosis by expression of IAP-antagonists, DNA-damaging agents and even knockdown of the IAP diap1. This resistance to apoptosis, however, is lost in wandering L3 animals after acquiring a heightened sensitivity to apoptotic triggers. This switch in sensitivity to death activators is mediated by a change in mechanisms available for activating endogenous caspases, from an apoptosome-independent to an apoptosome-dependent pathway. This switch in apoptotic pathways is regulated in a cell-autonomous manner by the steroid hormone ecdysone, through changes in expression of critical pro-, but not anti-, apoptotic genes. This steroid-controlled switch defines a novel, physiologically-regulated, mechanism for controlling sensitivity to apoptosis and provides new insights into the control of apoptosis during development.
Insights
Cell sensitivity to apoptosis is regulated during development. A steroid hormone switch in Drosophila controls this sensitivity, impacting developmental processes and disease.
Area of Science:
- Developmental Biology
- Cell Death Pathways
- Molecular Endocrinology
Background:
- Precise control of apoptosis is vital for organism development, tissue maintenance, and disease prevention.
- In Drosophila, apoptosis is triggered by IAP antagonists like reaper, hid, and grim, but sensitivity regulation is key.
- Developmental stage dictates cellular capacity to undergo apoptosis, establishing permissive or restrictive windows.
Purpose of the Study:
- To characterize a developmental switch in apoptosis sensitivity during Drosophila third-instar larval (L3) stage.
- To elucidate the molecular mechanisms underlying this shift from apoptosis resistance to sensitivity.
- To identify the regulatory role of steroid hormones in controlling apoptosis sensitivity.
Main Methods:
- Analysis of apoptosis induction in early versus wandering L3 Drosophila larvae using IAP antagonists, DNA-damaging agents, and IAP (diap1) knockdown.
- Investigation of caspase activation pathways, comparing apoptosome-dependent and -independent mechanisms.
- Assessment of ecdysone's role in regulating pro- and anti-apoptotic gene expression.
Main Results:
- Early L3 larvae exhibit high resistance to apoptosis induction, while wandering L3 larvae become highly sensitive.
- This switch is mediated by a transition from apoptosome-independent to apoptosome-dependent caspase activation.
- The steroid hormone ecdysone cell-autonomously regulates this sensitivity switch by altering pro-apoptotic gene expression.
Conclusions:
- A novel, physiologically regulated mechanism controls apoptosis sensitivity during Drosophila development.
- Steroid hormone signaling, specifically ecdysone, dictates cellular susceptibility to apoptotic triggers.
- This steroid-controlled switch provides critical insights into developmental apoptosis regulation and its implications for disease.
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