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Updated: Mar 14, 2026
A Simple Method for High Throughput Chemical Screening in Caenorhabditis Elegans
Published on: March 20, 2018
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.
Abstract:
Programmed cell death is a ubiquitous process in metazoan development. Apoptosis, one cell death form, has been studied extensively. However, mutations inactivating key mammalian apoptosis regulators do not block most developmental cell culling, suggesting that other cell death pathways are likely important. Recent work in the nematode Caenorhabditis elegans identified a non-apoptotic cell death form mediating the demise of the male-specific linker cell. This cell death process (LCD, linker cell-type death) is morphologically conserved, and its molecular effectors also mediate axon degeneration in mammals and Drosophila. To develop reagents to manipulate LCD, we established a simple high-throughput screening protocol for interrogating the effects of small molecules on C. elegans linker cell death in vivo. From 23,797 compounds assayed, 11 reproducibly block linker cell death onset. Of these, five induce animal lethality, and six promote a reversible developmental delay. These results provide proof-of principle validation of our screening protocol, demonstrate that developmental progression is required for linker cell death, and suggest that larger scale screens may identify LCD-specific small-molecule regulators that target the LCD execution machinery.
Insights
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.
