Abstract
The transforming growth factor beta superfamily encompasses a large family of ligands that are well conserved across many organisms. They are regulators of a number of physiological and pathological processes. The model nematode Caenorhabditis elegans has been instrumental in identifying key components of the transforming growth factor beta (TGFβ) pathway. In C. elegans, the TGFβ homolog DAF-7 signals through the DAF-1 Type I and DAF-4 Type II receptors to phosphorylate downstream R-SMADs DAF-8 and DAF-14. These R-SMADs translocate into the nucleus to inhibit Co-SMAD DAF-3. Many of the roles of the canonical DAF-7 pathway, involving both DAF-1 and DAF-3, have been identified using targeted genetic studies. Few have assessed the global transcriptomic changes in response to these genes, especially in adult animals. In this study, we performed RNA sequencing on wild type, daf-1, and daf-1; daf-3 adult hermaphrodites. To assess the overall trends of the data, we identified differentially expressed genes (DEGs) and performed gene ontology analysis to identify the types of downstream genes that are differentially expressed. Hierarchical clustering showed that the daf-1; daf-3 double mutants are transcriptionally more similar to wild type than daf-1 mutants. Analysis of the DEGs showed a disproportionally high number of genes whose expression is increased in daf-1 mutants, suggesting that DAF-1 acts as a general repressor of gene expression in wild type animals. Gene ontology analysis of the DEGs produced many significantly enriched terms, including Molting Cycle, Response to Topologically Incorrect Protein, and Response to Biotic Stimulus. Understanding the direct and indirect targets of the DAF-7 TGFβ pathway through this RNA-seq dataset can provide insight into novel roles of the multifunctional signaling pathway, as well as identify novel genes that may participate in previously reported functions of TGFβ signaling.
Highlights
Transforming growth factor beta (TGFβ) is the prototype of the large family of secreted ligands that act through downstream receptors to modulate diverse biological functions, such as embryological development, adult stem cell differentiation, immune regulation, wound healing, inflammation, and cancer [1,2,3,4,5,6]
In C. elegans, DAF-7 is a TGFβ and ishomolog highly that conserved among many organisms
TGFβ pathway signals through the and that is secreted by ASI sensory neurons in response to environmental cues, such as pheromones and DAF-4 Type II receptors to downstream DAF-8 and DAF-14
Summary
Transforming growth factor beta (TGFβ) is the prototype of the large family of secreted ligands that act through downstream receptors to modulate diverse biological functions, such as embryological development, adult stem cell differentiation, immune regulation, wound healing, inflammation, and cancer [1,2,3,4,5,6]. The functionality of this family of proteins is highly conserved among many organisms, including human, mice, nematodes, and flies [7,8,9]. While TGFβ has been shown to inhibit growth ofmechanisms, many cell types, such asdifferent, epithelialand [11,12], hematopoietic [13,14], and to developmental andthe pathologic revealing sometimes opposite, responses glial For cellsexample,
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