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Updated: Oct 17, 2025
In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila
Published on: November 27, 2016
Comparative transcriptomic analysis reveals gene regulation mediated by caspase activity in a chordate organism
Gabriel Krasovec1,2, Anthi Karaiskou3, Éric Quéinnec4
1Institut de Systématique, Evolution, Biodiversité (ISYEB), UMR 7205, Sorbonne Université, Muséum National d'histoire Naturelle, CNRS, EPHE, 7 Quai St-Bernard, F-75252, Paris Cedex 05, France. gabriel.krasovec@nuigalway.ie.
Background:
Apoptosis is a caspase regulated cell death present in all metazoans defined by a conserved set of morphological features. A well-described function of apoptosis is the removal of excessive cells during development and homeostasis. Recent studies have shown an unexpected signalling property of apoptotic cells, affecting cell fate and/or behaviour of neighbouring cells. In contrast to the apoptotic function of cell elimination, this new role of apoptosis is not well understood but seems caspase-dependent. To deepen our understanding of apoptotic functions, it is necessary to work on a biological model with a predictable apoptosis pattern affecting cell fate and/or behaviour. The tunicate Ciona intestinalis has a bi-phasic life cycle with swimming larvae which undergo metamorphosis after settlement. Previously, we have shown that the tail regression step during metamorphosis, characterized by a predictable polarized apoptotic wave, ensures elimination of most tail cells and controls primordial germ cells survival and migration.
Results:
We performed differential transcriptomic analysis between control metamorphosing larvae and larvae treated with the pan-caspase inhibitor Z-VAD-fmk in order to explore the transcriptional control of apoptotic cells on neighbouring cells that survive and migrate. When caspase activity was impaired, genes known to be involved in metamorphosis were downregulated along with other implicated in cell migration and survival molecular pathways.
Conclusion:
We propose these results as a confirmation that apoptotic cells can control surrounding cells fate and as a reference database to explore novel apoptotic functions in animals, including those related to migration and differentiation.
Insights
Apoptotic cells signal to control neighboring cell fate during tunicate metamorphosis. Inhibiting caspases disrupts gene expression for cell migration and survival, confirming apoptosis
Area of Science:
- Developmental Biology
- Cell Biology
- Molecular Biology
Background:
- Apoptosis, or programmed cell death, is a caspase-regulated process vital for development and homeostasis.
- Recent research reveals apoptotic cells possess signaling properties influencing neighboring cells' fate and behavior.
- The tunicate Ciona intestinalis offers a model with predictable apoptosis during metamorphosis, crucial for understanding these signaling roles.
Purpose of the Study:
- To investigate the transcriptional control exerted by apoptotic cells on surviving and migrating neighboring cells.
- To explore the caspase-dependent mechanisms underlying apoptosis-mediated cell fate and behavior modulation.
Main Methods:
- Differential transcriptomic analysis was conducted on Ciona intestinalis larvae.
- Larvae were compared between control groups and those treated with the pan-caspase inhibitor Z-VAD-fmk.
- This approach aimed to identify gene expression changes resulting from impaired caspase activity.
Main Results:
- Impaired caspase activity led to the downregulation of genes essential for metamorphosis.
- Key molecular pathways involved in cell migration and survival were also downregulated.
- These findings highlight the role of apoptosis in regulating gene expression in surrounding cells.
Conclusions:
- Apoptotic cells demonstrably control the fate of surrounding cells.
- The study provides a reference dataset for exploring novel apoptotic functions, including roles in migration and differentiation.
- These findings advance the understanding of apoptosis beyond cell elimination to cell communication and regulation.
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