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Published on: May 3, 2024
A collective form of cell death requires homeodomain interacting protein kinase
Nichole Link1, Po Chen, Wan-Jin Lu
1Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Abstract:
We examined post-eclosion elimination of the Drosophila wing epithelium in vivo where collective "suicide waves" promote sudden, coordinated death of epithelial sheets without a final engulfment step. Like apoptosis in earlier developmental stages, this unique communal form of cell death is controlled through the apoptosome proteins, Dronc and Dark, together with the IAP antagonists, Reaper, Grim, and Hid. Genetic lesions in these pathways caused intervein epithelial cells to persist, prompting a characteristic late-onset blemishing phenotype throughout the wing blade. We leveraged this phenotype in mosaic animals to discover relevant genes and establish here that homeodomain interacting protein kinase (HIPK) is required for collective death of the wing epithelium. Extra cells also persisted in other tissues, establishing a more generalized requirement for HIPK in the regulation of cell death and cell numbers.
Insights
This study reveals that Drosophila wing epithelial cells undergo coordinated "suicide waves" for elimination, controlled by key apoptosis proteins. Homeodomain interacting protein kinase (HIPK) is crucial for this collective cell death, impacting cell numbers.
Area of Science:
- Developmental Biology
- Cell Death Mechanisms
- Drosophila melanogaster Research
Background:
- Epithelial tissue elimination is crucial during development.
- Apoptosis, a programmed cell death, is well-studied in early development.
- A unique form of collective cell death in the Drosophila wing epithelium was previously observed.
Purpose of the Study:
- To investigate the molecular mechanisms of post-eclosion epithelial cell death in the Drosophila wing.
- To identify novel genes involved in this collective cell death process.
- To understand the role of homeodomain interacting protein kinase (HIPK) in regulating cell death and cell numbers.
Main Methods:
- In vivo examination of Drosophila wing epithelium.
- Genetic analysis of apoptosis pathway components (Dronc, Dark, Reaper, Grim, Hid).
- Utilizing mosaic animals and a late-onset blemishing phenotype to screen for relevant genes.
Main Results:
- Collective "suicide waves" mediate coordinated epithelial sheet death without engulfment.
- Genetic defects in apoptosis pathways lead to cell persistence and a blemishing phenotype.
- Homeodomain interacting protein kinase (HIPK) was identified as essential for collective wing epithelial cell death.
Conclusions:
- The Drosophila wing epithelium undergoes a unique, coordinated cell death process regulated by conserved apoptosis machinery.
- HIPK plays a critical role in this collective cell death and in controlling cell numbers across multiple tissues.
- This research uncovers a novel function for HIPK in regulating cell death and tissue homeostasis.
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