Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from the starved first larval stage (L1) C. elegans animals that were incubated in S-basal buffer for 30 hours after bleaching

ABSTRACT: How animals coordinate gene expression in response to starvation is an outstanding problem closely linked to aging, obesity, and cancer. Newly hatched Caenorhabditis elegans respond to food deprivation by halting development and promoting long-term survival (L1 diapause), thereby providing an excellent model to study starvation response. Through a genetic search, we have discovered that the tumor suppressor Rb critically promotes survival during L1 diapause and likely does so by regulating the expression of genes in both insulin-IGF-1 signaling (IIS)-dependent and -independent pathways mainly in neurons and the intestine. Global gene expression analyses suggested that Rb maintains the M-bM-^@M-^\starvation-induced transcriptomeM-bM-^@M-^] and represses the M-bM-^@M-^\re-feeding induced transcriptomeM-bM-^@M-^], including the repression of many pathogen/toxin/oxidative stress-inducible and metabolic genes, as well as the activation of many other stress-resistant genes, mitochondrial respiratory chain genes, and potential IIS receptor antagonists. Notably, the majority of genes dysregulated in starved L1 Rb(-) animals were not found to be dysregulated in fed conditions. Together, these findings identify Rb as a critical regulator of the starvation response and suggest a link between functions of tumor suppressors and starvation survival. These results may provide mechanistic insights into why cancer cells are often hypersensitive to starvation treatment. Gravid C. elegans adult animals were bleached with hypochlorite and sodium hydroxide. The resulting eggs were hatched in 8M-bM-^@M-^S10 mL S-basal without cholesterol in 15-mL conical tubes, which were placed on an end-over-end rocker (VWR) at 20 M-BM-0C. 30 hours later, starved L1s were collected for RNA preparations. Wild type and lin-35/Rb mutant were profiled in triplicate. All replicates were biological replicates.

ORGANISM(S): Caenorhabditis elegans

SUBMITTER: Mingxue Cui

PROVIDER: E-GEOD-45651 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The tumor suppressor Rb critically regulates starvation-induced stress response in C. elegans.

Cui Mingxue M Cohen Max L ML Teng Cindy C Han Min M

Current biology : CB 20130509 11

How animals coordinate gene expression in response to starvation is an outstanding problem closely linked to aging, obesity, and cancer. Newly hatched Caenorhabditis elegans respond to food deprivation by halting development and promoting long-term survival (L1 diapause), thereby providing an excellent model for the study of starvation response. Through a genetic search, we have discovered that the tumor suppressor Rb critically promotes survival during L1 diapause and most likely does so by reg ...[more]

PMID: 23664972

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Project description:Post-embryonic development of the nematode C. elegans is governed by nutrient availability. L1-stage larvae remain in a state of developmental arrest after hatching until they feed. This “L1 arrest” (or "L1 diapause") is associated with increased stress resistance, supporting starvation survival. Loss of the transcription factor daf-16/FOXO, an effector of insulin/IGF signaling, results in arrest-defective and starvation-sensitive phenotypes. We show that daf-16/FOXO regulates L1 arrest cell-nonautonomously, suggesting that insulin/IGF signaling regulates at least one additional signaling pathway. We used mRNA-seq to identify candidate signaling molecules affected by daf-16/FOXO during L1 arrest. daf-16/FOXO had overlapping but distinct effects on gene expression in L1 arrest compared to daf-2/InsR adults. Notably, dbl-1/TGF-β, a ligand for the Sma/Mab pathway, and daf-36, which encodes an upstream component of the daf-12/NHR steroid hormone signaling pathway, were up-regulated during L1 arrest in a daf-16/FOXO mutant. Using genetic epistasis analysis, we show that dbl-1/TGF-β and daf-12/NHR steroid hormone signaling pathways are required for the daf-16/FOXO arrest-defective phenotype, suggesting that daf-16/FOXO represses dbl-1/TGF-β and daf-36. The dbl-1/TGF-β and daf-12/NHR pathways have not previously been shown to affect L1 development, but we found that disruption of these pathways delayed L1 development in fed larvae, consistent with these pathways promoting development in starved daf-16/FOXO mutants. Though the dbl-1/TGF-β and daf-12/NHR pathways are epistatic to daf-16/FOXO for the arrest-defective phenotype, disruption of these pathways does not suppress starvation sensitivity of daf-16/FOXO mutants. This observation uncouples starvation survival from developmental arrest, indicating that DAF-16/FOXO targets distinct effectors for each phenotype, and revealing that inappropriate development during starvation does not cause the early demise of daf-16/FOXO mutants. Overall, this study shows that daf-16/FOXO promotes developmental arrest cell-nonautonomously by repressing pathways that promote larval development.

Dataset Information

Expression data from the starved first larval stage (L1) C. elegans animals that were incubated in S-basal buffer for 30 hours after bleaching

Publications

The tumor suppressor Rb critically regulates starvation-induced stress response in C. elegans.

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