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Quantification of Information Encoded by Gene Expression Levels During Lifespan Modulation Under Broad-range Dietary Restriction in C. elegans
Published on: August 16, 2017
DAF-16-dependent and independent expression targets of DAF-2 insulin receptor-like pathway in Caenorhabditis elegans
1Molecular Biology Program and Division of Biogerontology, University of Southern California, Los Angeles, CA 90089, USA.
Abstract:
The daf-2 insulin-like receptor pathway regulates development and life-span in Caenorhabditis elegans. Reduced DAF-2 signaling leads to changes in downstream targets via the daf-16 gene, a fork-head transcription factor which is regulated by DAF-2, and results in extended life-span. Here, we describe the first identification of genes whose expression is controlled by the DAF-2 signaling cascade. dao-1, dao-2, dao-3, dao-4, dao-8 and dao-9 are down-regulated in daf-2 mutant adults compared to wild-type adults, whereas dao-5, dao-6 and dao-7 are up-regulated. The latter genes are negatively regulated by DAF-2 signaling and positively regulated by DAF-16. Positive regulation by DAF-2 on dao-1, dao-4 and dao-8 was mediated by DAF-16, whereas daf-16 mediates only part of DAF-2 signaling for dao-2 and dao-9. Regulation by DAF-2 is most likely DAF-16 independent for dao-3 and hsp-90. RNA levels of dao-5 and dao-6 showed elevated expression in daf-2 adults, as well as being strongly expressed in dauer larvae. In contrast, hsp-90 transcript levels are low in daf-2 mutant adults though they are enriched in dauer larvae, indicating overlapping but not identical mechanisms of efficient life maintenance in stress-resistant dauer larvae and long-lived daf-2 mutant adults. dao-1, dao-8 and dao-9 are homologs of the FK506 binding proteins that interact with the mammalian insulin pathway. dao-3 encodes a putative methylenetetrahydrofolate dehydrogenase. DAO-5 shows 33 % identity with human nucleolar phosphoprotein P130. dao-7 is similar to the mammalian ZFP36 protein. Distinct regulatory patterns of dao genes implicate their diverse positions within the signaling network of DAF-2 pathway, and suggest they have unique contributions to development, metabolism and longevity.
Insights
Researchers identified novel genes regulated by the DAF-2 insulin pathway in C. elegans. These genes, including dao-1 to dao-9, show varied expression patterns impacting development and longevity.
Area of Science:
- Genetics and Molecular Biology
- Aging Research
- Developmental Biology
Background:
- The DAF-2 insulin-like receptor pathway is crucial for regulating development and lifespan in *Caenorhabditis elegans*.
- Reduced DAF-2 signaling extends lifespan, partly through the fork-head transcription factor DAF-16.
- Understanding downstream targets of DAF-2 is key to deciphering aging mechanisms.
Purpose of the Study:
- To identify and characterize genes directly controlled by the DAF-2 signaling cascade.
- To elucidate the regulatory roles of DAF-2 and DAF-16 in gene expression.
- To explore the functional implications of these genes in development and longevity.
Main Methods:
- Gene expression analysis in *daf-2* mutant versus wild-type *C. elegans* adults.
- Identification of differentially expressed genes (dao genes).
- Analysis of DAF-16 dependency for DAF-2 regulation of target genes.
Main Results:
- DAO-1, DAO-2, DAO-3, DAO-4, DAO-8, and DAO-9 are down-regulated in *daf-2* mutants.
- DAO-5, DAO-6, and DAO-7 are up-regulated in *daf-2* mutants and positively regulated by DAF-16.
- DAF-16 mediates DAF-2 signaling for some genes (e.g., dao-1, dao-4, dao-8) but not others (e.g., dao-3, hsp-90).
- DAO-5 and DAO-6 expression is elevated in *daf-2* adults and dauer larvae, while hsp-90 shows differential regulation.
Conclusions:
- The study identifies novel downstream targets of the DAF-2 pathway, expanding our understanding of its regulatory network.
- Distinct regulatory patterns of *dao* genes suggest diverse roles in development, metabolism, and longevity.
- These findings highlight the complex interplay between insulin signaling, transcription factors, and aging processes.
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