| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
In a response to unfavorable growth conditions, the nematode Caenorhabditis elegans ceases development and enters a diapause stage. C.elegans utilizes the diapause-inducing pheromone as a chemical mediator to detect overpopulation. The insulin/insulin-like growth factor-I signaling (IIS) pathway of C.elegans regulates not only larval diapause but also adult lifespan via the receptor DAF-2. Recently, it was reported that ins-7 RNAi knockdown causes an extended lifespan. In our previous study, we identified insulin-like genes ins-17 and ins-18 and disrupted them to elucidate their physiological functions. In the presence of the pheromone described above, these gene-disruptions caused a significant decrease in larval diapause. In contrast, effect of the disruptions on lifespan has been ambiguous. Under the background described above, we attempted to characterize the diapause-inducing pheromone. In addition, we elucidated physiological functions of these insulin-like genes in diapause-indu
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cing and lifespan-extending conditions.
We first characterized the diapause-inducing pheromone chemically and biologically. We tried purifying the pheromone with several chromatographic methods including HPLC. Although the purification has not yet completed, the pheromone seems a neutral or basic compound of which molecular weight is around 1,000. Quite interestingly, the crude pheromone caused an extended lifespan in a dose-dependent manner. In addition, the lifespan extension depended on the transcription factor DAF-16 downstream of DAF-2, suggesting that the pheromone regulates adult lifespan via the IIS pathway.
Next, we disrupted insulin-like genes ins-7 and ins-11. As expected, the mutant animal lacking ins-7 showed an extended lifespan. The animal also revealed an increase in larval diapause in the presence of the pheromone. In contract, the gene-disruption of ins-11 showed no influence in larval diapause and adult lifespan. Then in order to elucidate redundant function of ins genes, we crossed the gene-disrupted animals. Disruption of ins-11, ins-17, or ins-18 suppressed the larval diapause caused by that of ins-7, indicating that ins-11, -17, and -18 genes have an opposite function to ins-7. Moreover, only disruption of ins-18 canceled the lifespan extension caused by that of ins-7, indicating that only ins-18 has an opposite function to ins-7 in lifespan regulation. In short, INS-7 functions as an agonist to the receptor DAF-2, and INS-11, -17, and -18 function as an antagonist in terms of larval diapause. On the other hand, only INS-18 functions as an antagonist to DAF-2 in terms of adult lifespan. Less
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