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Updated: May 5, 2026
Using Caenorhabditis elegans to Screen for Tissue-Specific Chaperone Interactions
Published on: June 7, 2020
Uncovering buffered pleiotropy: a genome-scale screen for mel-28 genetic interactors in Caenorhabditis elegans
Anita G Fernandez1, Emily K Mis, Allison Lai
1Fairfield University Biology Department, Fairfield, Connecticut 06824.
Abstract:
mel-28 (maternal-effect-lethal-28) encodes a conserved protein required for nuclear envelope function and chromosome segregation in Caenorhabditis elegans. Because mel-28 is a strict maternal-effect lethal gene, its function is required in the early embryo but appears to be dispensable for larval development. We wanted to test the idea that mel-28 has postembryonic roles that are buffered by the contributions of other genes. To find genes that act coordinately with mel-28, we did an RNA interference-based genetic interaction screen using mel-28 and wild-type larvae. We screened 18,364 clones and identified 65 genes that cause sterility in mel-28 but not wild-type worms. Some of these genes encode components of the nuclear pore. In addition we identified genes involved in dynein and dynactin function, vesicle transport, and cell-matrix attachments. By screening mel-28 larvae we have bypassed the requirement for mel-28 in the embryo, uncovering pleiotropic functions for mel-28 later in development that are normally provided by other genes. This work contributes toward revealing the gene networks that underlie cellular processes and reveals roles for a maternal-effect lethal gene later in development.
Insights
Maternal-effect-lethal-28 (mel-28) protein is essential for early development but also has hidden roles later in life. A genetic screen revealed new genes that work with mel-28, uncovering its broader functions.
Area of Science:
- Genetics
- Developmental Biology
- Molecular Biology
Background:
- The mel-28 gene is crucial for nuclear envelope integrity and chromosome segregation in early C. elegans embryos.
- mel-28 is a maternal-effect lethal gene, meaning its absence is lethal in the embryo, masking potential roles in later development.
Purpose of the Study:
- To investigate potential postembryonic functions of mel-28 that are masked by its essential embryonic role.
- To identify genes that function alongside mel-28 to uncover its broader developmental roles.
Main Methods:
- Conducted an RNA interference (RNAi)-based genetic interaction screen in mel-28 mutant larvae.
- Screened 18,364 clones to identify genes that cause sterility specifically in mel-28 mutant worms.
Main Results:
- Identified 65 genes that interact with mel-28, including components of the nuclear pore, dynein/dynactin machinery, vesicle transport, and cell-matrix adhesion.
- Demonstrated that mel-28 has pleiotropic functions beyond early embryogenesis, which are compensated for by other genes in wild-type worms.
Conclusions:
- Bypassing the embryonic lethality of mel-28 revealed its critical roles in postembryonic development.
- This study illuminates gene networks involved in fundamental cellular processes and highlights previously unrecognized functions of maternal-effect genes.
