The highly conserved target-of-rapamycin (TOR) protein kinases control cell growth in response to nutrients and growth factors. In mammals, TOR has been shown to interact with raptor to relay nutrient signals to downstream translation machinery. We report that in C. elegans, mutations in the genes encoding CeTOR and raptor result in dauer-like larval arrest, implying that CeTOR regulates dauer diapause. The daf-15 (raptor) and let-363 (CeTOR) mutants shift metabolism to accumulate fat, and raptor mutations extend adult life span. daf-15 transcription is regulated by DAF-16, a FOXO transcription factor that is in turn regulated by daf-2 insulin/IGF signaling. This is a new mechanism that regulates the TOR pathway. Thus, DAF-2 insulin/IGF signaling and nutrient signaling converge on DAF-15 (raptor) to regulate C. elegans larval development, metabolism and life span.
The Caenorhabditis elegans dauer larva is specialized for dispersal without growth and is formed under conditions of overcrowding and limited food. The daf-7 gene, required for transducing environmental cues that support continuous development with plentiful food, encodes a transforming growth factor-beta (TGF-beta) superfamily member. A daf-7 reporter construct is expressed in the ASI chemosensory neurons. Dauer-inducing pheromone inhibits daf-7 expression and promotes dauer formation, whereas food reactivates daf-7 expression and promotes recovery from the dauer state. When the food/pheromone ratio is high, the level of daf-7 mRNA peaks during the L1 larval stage, when commitment to non-dauer development is made.
The dauer larva of Caenorhabditis elegans is a developmentally arrested stage induced by starvation or overcrowding. Mutant genes controlling the ability to form dauer larvae interact in a way which allows them to be ordered in a pathway. Mutant phenotypes suggest that the pathway corresponds to neural processing of environmental stimuli.
A Caenorhabditis-specific pheromone and the food supply influence both entry into and exit from a developmentally arrested juvenile stage called the dauer larva. The pheromone increases the frequency of dauer larva formation and inhibits recovery but does not affect adult behavior such as chemotaxis and egg laying. The fatty acid--like pheromone has been partially purified and characterized by a new bioassay. If similar developmental control mechanisms are used by parasitic nematodes, such mechanisms might be exploited to develop highly selective anthelmintic agents.
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