Transcriptomic Profiling of DAF-7/TGFβ Pathway Mutants in C. elegans.

Area of Science:

• Developmental Biology
• Molecular Biology
• Genetics

Background:

• The transforming growth factor beta (TGFβ) superfamily regulates diverse physiological and pathological processes.
• The nematode *Caenorhabditis elegans* is a key model for dissecting the TGFβ pathway, involving DAF-7 ligand, DAF-1/DAF-4 receptors, and DAF-8/DAF-14 R-SMADs.
• While roles of the canonical DAF-7 pathway are known, global transcriptomic changes, especially in adults, remain underexplored.

Purpose of the Study:

• To investigate the global transcriptomic impact of the TGFβ pathway in adult *C. elegans*.
• To identify downstream targets and regulatory roles of DAF-1 and DAF-3 in gene expression.
• To provide insights into novel functions of the TGFβ signaling pathway.

Main Methods:

• RNA sequencing was performed on wild type, *daf-1* single mutants, and *daf-1*; *daf-3* double mutant adult hermaphrodites.
• Differentially expressed genes (DEGs) were identified and analyzed using gene ontology (GO) analysis.
• Hierarchical clustering was used to compare transcriptional profiles of the different genotypes.

Main Results:

• Hierarchical clustering indicated that *daf-1*; *daf-3* double mutants exhibit transcriptional profiles more similar to wild type than *daf-1* single mutants.
• A disproportionately high number of genes showed increased expression in *daf-1* mutants, suggesting DAF-1 acts as a general repressor.
• GO analysis revealed significantly enriched terms including Molting Cycle, Response to Topologically Incorrect Protein, and Response to Biotic Stimulus.

Conclusions:

• DAF-1 plays a significant role in repressing gene expression in adult *C. elegans*.
• The DAF-7 TGFβ pathway influences fundamental processes such as molting and responses to biotic stimuli.
• This RNA-seq dataset offers a valuable resource for understanding novel roles and targets of TGFβ signaling.