The humble fruit fly, Drosophila melanogaster, is an important model system, boasting facile genetics, complex organ systems, complex behaviors and a sequenced genome. Our long-term interest has been in determining how the sex of the germ line is established. In other words, how a germ line stem cell gives rise to either sperm or eggs. Stem cell development occurs in a defined niche. Our work suggests that when a male stem cell develops in a female niche a tumor results, while when a female stem cell develops in a male environment, stem cell proliferation or survival is poor. Microarray analysis shows that stem cell tumors forming due to inappropriate juxtaposition of male germ cells in a female soma are similar to tumors resulting from mutations in any of several genes required for female fertility. These results confirm our longstanding proposition that the proteins encoded by these genes play important roles in germline sex determination. We are also using microarray technology to identify diagnostic markers for germ line stem cells of the two sexes and are exploring the peculiar nature of the X chromosome, dosage compensation in particular. Array work is being extended to other species in the Drosophila genus. ? ? One of the advantages of working on a model organism at the NIH is exposure to scientists interested in a range of topics, from basic research, to insect disease vectors, or translational and clinical studies. We have also participated in the NIH multiple endocrine neoplasia type-1 (MEN1) consortium led by Francis Collins (NHGRI), Steve Marx, and Allen Spiegel (both NIDDK). We have determined that Drosophila MEN1 can act to negatively regulate the jun/fos complex, AP1. It is our hope that fruit fly studies will provide a skeletal view of gene regulation pathways to be fleshed out by research on mammalian systems.
Chen, Zhen-Xia; Sturgill, David; Qu, Jiaxin et al. (2014) Comparative validation of the D. melanogaster modENCODE transcriptome annotation. Genome Res 24:1209-23 |
Malone, John; Oliver, Brian (2009) The genomic 'inner fish' and a regulatory enigma in the vertebrates. J Biol 8:32 |
Malone, John H; Oliver, Brian (2008) The sex chromosome that refused to die. Bioessays 30:409-11 |
Larracuente, Amanda M; Sackton, Timothy B; Greenberg, Anthony J et al. (2008) Evolution of protein-coding genes in Drosophila. Trends Genet 24:114-23 |
Zhang, Yu; Sturgill, David; Parisi, Michael et al. (2007) Constraint and turnover in sex-biased gene expression in the genus Drosophila. Nature 450:233-7 |
Zhang, Yu; Oliver, Brian (2007) Dosage compensation goes global. Curr Opin Genet Dev 17:113-20 |
Kalamegham, Rasika; Sturgill, David; Siegfried, Esther et al. (2007) Drosophila mojoless, a retroposed GSK-3, has functionally diverged to acquire an essential role in male fertility. Mol Biol Evol 24:732-42 |
Sturgill, David; Zhang, Yu; Parisi, Michael et al. (2007) Demasculinization of X chromosomes in the Drosophila genus. Nature 450:238-41 |
Oliver, Brian (2006) Tiling DNA microarrays for fly genome cartography. Nat Genet 38:1101-2 |
Gupta, Vaijayanti; Parisi, Michael; Sturgill, David et al. (2006) Global analysis of X-chromosome dosage compensation. J Biol 5:3 |
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