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Programmed cell death in Drosophila
H Steller1, J M Abrams, M E Grether
1Howard Hughes Medical Institute, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.
Abstract:
During Drosophila development, large numbers of cells undergo natural cell death. Even though the onset of these deaths is controlled by many different signals, most of the dying cells undergo common morphological and biochemical changes that are characteristic of apoptosis in vertebrates. We have surveyed a large fraction of the Drosophila genome for genes that are required for programmed cell death by examining the pattern of apoptosis in embryos homozygous for previously identified chromosomal deletions. A single region on the third chromosome (in position 75C1,2) was found to be essential for all cell deaths that normally occur during Drosophila embryogenesis. We have cloned the corresponding genomic DNA and isolated a gene, reaper, which is capable of restoring apoptosis when reintroduced into cell death defective deletions. The reaper gene is specifically expressed in cells that are doomed to die, and its expression precedes the first morphological signs of apoptosis by 1-2 h. This gene is also rapidly induced upon X-ray irradiation, and reaper deletions offer significant protection against radiation-induced apoptosis. Our results suggest that reaper represents a key regulatory switch for the activation of apoptosis in response to a variety of distinct signals.
Insights
Researchers identified the "reaper" gene as a crucial regulator for programmed cell death (apoptosis) in Drosophila development. This gene activates apoptosis in response to various signals, acting as a key switch for cell death.
Area of Science:
- Developmental Biology
- Genetics
- Cell Biology
Background:
- Programmed cell death, or apoptosis, is essential during Drosophila development.
- Dying cells exhibit conserved morphological and biochemical changes similar to vertebrate apoptosis.
Purpose of the Study:
- To identify genes essential for programmed cell death in Drosophila.
- To understand the genetic regulation of apoptosis during embryogenesis.
Main Methods:
- Genome-wide survey of Drosophila deletions to identify apoptosis-defective mutants.
- Cloning and functional analysis of candidate genes.
- Gene expression analysis and radiation-induced apoptosis assays.
Main Results:
- A single locus on the third chromosome (75C1,2) is critical for all developmental apoptosis.
- The "reaper" gene was isolated and shown to restore apoptosis.
- Reaper expression precedes apoptotic morphological changes and is induced by X-ray irradiation.
Conclusions:
- Reaper acts as a key regulatory switch for initiating apoptosis in Drosophila.
- This gene is involved in both developmental and stress-induced apoptosis.
- Understanding reaper provides insights into conserved mechanisms of programmed cell death.