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A Simple Method for High Throughput Chemical Screening in Caenorhabditis Elegans
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A High-Throughput Small Molecule Screen for C. elegans Linker Cell Death Inhibitors.
Andrew R Schwendeman1, Shai Shaham1
1Laboratory of Developmental Genetics, The Rockefeller University, New York, New York, United States of America.
Plos One
|October 8, 2016
Summary
Researchers screened 23,797 compounds to find molecules affecting programmed cell death in C. elegans. Six compounds were identified that reversibly delay development by blocking linker cell-type death (LCD).
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Programmed cell death is crucial for metazoan development, with apoptosis being extensively studied.
- However, non-apoptotic cell death pathways are likely involved in developmental cell culling, as apoptosis-mutant studies show.
- A non-apoptotic cell death, linker cell-type death (LCD), was identified in Caenorhabditis elegans, mediating linker cell demise.
Purpose of the Study:
- To establish a high-throughput screening protocol for identifying small molecules that modulate LCD in vivo.
- To develop chemical reagents for manipulating LCD and its underlying molecular machinery.
- To investigate the role of developmental progression in LCD.
Main Methods:
- A high-throughput screening protocol was developed to assay small molecules for their effects on C. elegans linker cell death.
- 23,797 compounds were screened in vivo.
- Compounds were evaluated for their ability to block LCD onset and their impact on animal lethality and development.
Main Results:
- The screen identified 11 compounds that reproducibly block linker cell death onset from 23,797 tested.
- Five of these compounds induced animal lethality.
- Six compounds promoted a reversible developmental delay, indicating modulation of LCD.
Conclusions:
- The screening protocol is validated as effective for identifying modulators of LCD.
- Developmental progression is a prerequisite for linker cell death.
- Larger-scale screens hold promise for discovering specific regulators of the LCD execution machinery.
