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Comments on Suchanek, Monika et al. (2011) International Worm Meeting "The germline influences C. elegans' longevity through Wnt signaling." (0)
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Suchanek, Monika, & Kenyon, Cynthia (2011). The germline influences C. elegans' longevity through Wnt signaling presented in International Worm Meeting. Unpublished information; cite only with author permission.
Germ cell ablation extends the life span of C. elegans by up to 60%. This effect is not due to sterility, as the removal of the entire reproductive system does not prolong life span. Similarly, the reproductive tissues of flies and mice control their lifespan. These findings are very exciting, because they suggest evolutionary conservation of the pathway linking reproductive status of the organism to its longevity. In C. elegans, the life-prolonging effect of germline ablation depends on the nuclear translocation of the DAF-16/FOXO transcription factor in intestinal cells, illustrating the existence of long-range communication between gonad and other organs. In intestinal nuclei, DAF-16 activates the transcription of multiple life-span extending genes. To understand how the intestine senses the absence of the germline, I screened a signaling component of the C. elegans genome for RNAi clones clones that interfere with germline signaling in C. elegans, utilizing both the subcellular localization of DAF-16::GFP in the intestine, as well as the intensity of fluorescence of a DAF-16 downstream target gene (SOD-3::GFP) in the germline-defective glp-1 worms. Screening of 1304 RNAi clones led to identification of 115 (8.8%) potential signal candidates. Among the genes that robustly affected DAF-16 localization and SOD-3 expression were multiple components of a Wnt-signaling pathway, suggesting the intriguing possibility that a Wnt signal communicates the status of the reproductive system to the rest of the organism. To identify the Wnt/b-catenin that functions to signal to the intestine in response to germline loss, I tested effects of all C. elegans Wnts and b-catenins on DAF-16 localization, SOD-3 expression, and lifespan. RNAi against wrm-1 (b-catenin) and mom-2 (Wnt) specifically affected the lifespan of animals lacking germ cells (and not that of other long-lived mutants or wild-type worms), therefore genetically behaving as expected for the signal to intestine. Both wrm-1 and mom-2 are components of a non-canonical Wnt signaling pathway that during C. elegans' development mediates communication between two early blastomeres (P2 and EMS) at the 4-cell stage. Interestingly, the blastomere EMS is the precursor of the intestine and P2 becomes the germline, raising an intriguing possibility that the same pathway that is used during development is later on during the adulthood reused to signal the status of the reproductive system to the intestine.
Affiliation:
- Dept of Biochemistry & Biophysics, University of California San Francisco