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A rapid increase in size is a major characteristic of larval development in Drosophila melanogaster . Such growth presumably requires the concomitant production of membrane lipids and is also accompanied by a significant accumulation of neutral lipid stores . Growing larvae must accumulate fatty acids to permit the synthesis of these lipids . Interestingly , wild type Drosophila can grow in the complete absence of exogenous fatty acids . This dissertation reports the finding that a lipogenic transcription factor , dSREBP (Drosophila Sterol Regulatory Element Binding Protein ) , is essential for the maintenance of this prototrophy . Drosophila larvae lacking dSREBP demonstrate a profound growth deficit in the second instar and die before reaching third instar . This is accompanied by transcriptional deficits in fatty acid synthetic genes . The growth deficit and lethality can be reversed by supplementing the culture medium with fatty acids . The most effective fatty acid , oleate , rescues 80 percent of dSREBP mutants to adulthood . Thus , a lack of dSREBP renders larvae auxotrophic for fatty acids . A reporter system demonstrates that dSREBP is active in tissues known to be involved in lipid metabolism - the fat body , oenocytes and anterior midgut . Finally , as expected of an end -product inhibited metabolic pathway , dSREBP activity can be suppressed by dietary supplementation with lipids . Thus , the dSREBP pathway coordinates endogenous synthesis with the dietary provision of exogenous lipids . These results establish Drosophila as a viable model for the genetic study of the SREBP pathway and provide the first evidence that , at an organismal level , the essential role of the pathway is the accumulation of lipids . The auxotrophic mutants and other reagents described here should be useful tools for further study of the SREBP pathway in particular and fatty acid metabolism in general . |
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