A Mosaic Genetic Screen for Drosophila Neoplastic Tumor Suppressor Genes Based on Defective Pupation

Genetics - Tập 177 Số 3 - Trang 1667-1677 - 2007
Laurent Menut1, Thomas Vaccari1, Heather Dionne1, Joseph A. Hill1, Geena X. Wu1, David Bilder1
1Department of Molecular and Cell Biology, University of California, Berkeley, California 94720

Tóm tắt

AbstractThe Drosophila neoplastic tumor suppressor genes (TSGs) coordinately control cell polarity and proliferation in epithelial and neuronal tissues. While a small group of neoplastic TSG mutations have been isolated and their corresponding genes cloned, the regulatory pathways that normally prevent inappropriate growth remain unclear. Identification of additional neoplastic TSGs may provide insight into this question. We report here the design of an efficient screen for isolating neoplastic TSG mutations utilizing genetically mosaic larvae. This screen is based on a defective pupation phenotype seen when a single pair of imaginal discs is homozygous for a neoplastic TSG mutation, which suggests that continuously proliferating cells can interfere with metamorphosis. Execution of this screen on two chromosome arms led to the identification of mutations in at least seven new neoplastic TSGs. The isolation of additional loci that affect hyperplastic as well as neoplastic growth indicates the utility of this screening strategy for studying epithelial growth control.

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Tài liệu tham khảo

2007, Cell, 128, 961, 10.1016/j.cell.2007.02.024

2007, Dev. Biol., 303, 625, 10.1016/j.ydbio.2006.12.001

2000, Nature, 403, 676, 10.1038/35001108

2000, Science, 289, 113, 10.1126/science.289.5476.113

2003, EMBO J., 22, 5769, 10.1093/emboj/cdg548

1984, Q. Rev. Biol., 59, 387, 10.1086/414040

2005, Curr. Biol., 15, 1785, 10.1016/j.cub.2005.09.011

2005, PLoS Biol., 3, e59, 10.1371/journal.pbio.0030059

1993

2006, Nat. Rev. Genet., 7, 907, 10.1038/nrg1989

1967, Am. Zool., 7, 760

1969, Natl. Cancer Inst. Monogr., 31, 365

1997, Genes Dev., 11, 2532, 10.1101/gad.11.19.2532

2006, Annu. Rev. Genet., 40, 335, 10.1146/annurev.genet.39.073003.100738

2006, Development, 133, 1871, 10.1242/dev.02356

2005, EMBO Rep., 6, 836, 10.1038/sj.embor.7400500

1987, Cell, 50, 215, 10.1016/0092-8674(87)90217-0

1995, Genes Dev., 9, 534, 10.1101/gad.9.5.534

2005, Nat. Cell Biol., 7, 1232, 10.1038/ncb1324

2005, Dev. Cell, 9, 699, 10.1016/j.devcel.2005.09.018

2000, Development, 127, 851, 10.1242/dev.127.4.851

2003, Dev. Cell, 4, 95, 10.1016/S1534-5807(02)00400-8

2003, Science, 302, 1227, 10.1126/science.1088474

2007, Genes Dev., 21, 886, 10.1101/gad.1536007

1988, Dev. Biol., 127, 392, 10.1016/0012-1606(88)90326-0

2004, Mol. Cell. Biol., 24, 6676, 10.1128/MCB.24.15.6676-6689.2004

1980, J. Embryol. Exp. Morphol., 57, 155

2007, Proc. Natl. Acad. Sci. USA, 104, 2721, 10.1073/pnas.0611666104

1972, Dev. Biol., 27, 71, 10.1016/0012-1606(72)90113-3

2003, Oncogene, 22, 6436, 10.1038/sj.onc.1206820

1999, Genetics, 152, 1631, 10.1093/genetics/152.4.1631

1999, Nat. Genet., 21, 177, 10.1038/5960

2005, Dev. Cell, 9, 711, 10.1016/j.devcel.2005.09.020

2006, EMBO J., 25, 5294, 10.1038/sj.emboj.7601401

2005, Proc. Natl. Acad. Sci. USA, 102, 13123, 10.1073/pnas.0504170102

2005, Dev. Cell, 9, 687, 10.1016/j.devcel.2005.09.019

1991, Cell, 66, 451, 10.1016/0092-8674(81)90009-X

1997, Dev. Genet., 20, 111, 10.1002/(SICI)1520-6408(1997)20:2<111::AID-DVG4>3.0.CO;2-A

1995, Development, 121, 1053, 10.1242/dev.121.4.1053

2004, J. Cell Biol., 167, 1137, 10.1083/jcb.200407158

2006, Genes Dev., 20, 1899, 10.1101/gad.1426906

1993, Dev. Biol., 156, 117, 10.1006/dbio.1993.1063