UC Riverside

During development organisms must decide whether to utilize energy or whether to store it. Previous work in Maduro lab has found evidence that early in the intestinal development there is a critical stage in which the timely activation of the transcription factor network, required for the development of the intestine establishes a mode of energy utilization, aimed at maximizing the production of progeny. When gut specification is compromised, by mutating transcription factors required for intestinal development, this changes the metabolism and physiology of those animals and they start to store energy even when the food is abundant. In this thesis, the phenotype associated with the compromised gut specification strains that we call Hypomorphic Gut Specification (HGS) strains is described. Also work was done to look at genes that are differentially expressed in HGS animals and two paralogous, reciprocally expressed genes in wild-type and HGS animals – fstr-1 and fstr-2 were characterized. Mutants were generated for fstr-1 and fstr-2 genes, and a double fstr-1,2 mutant. The specific phenotypes associated with those mutations were described. Results show that animals in which fstr-2 gene is deleted in otherwise normal genetic background, show characteristics associated with caloric restriction – enlarged intestinal lumen, increased size of lipid droplets, increased amount of gut granules. These phenotypes are similar to those observed in HGS strains. In addition, a reduced brood count, increased lifespan of fstr-2 mutants and increased resistance to toxins from Pseudomonas aeruginosa PA14 were observed. The double fstr-1,2 mutant phenotype is similar to the one of fstr-2 mutant. The expression of the fstr genes was also examined. Fstr-1 appears to be a stress response gene, as it has low expression under normal conditions and increased in HGS strains and in caloric restriction. FSTR-2 appears to be a plasma membrane protein expressed mostly in the intestinal cells and based on the conditions in some neurons and muscle cells. These results provide insight about the functions of some of the genes differentially expressed, downstream of improper gut specification, and how they might modulate the metabolism of C. elegans and the switch from energy utilization mode to energy storage mode.