Targeted gene expression in Drosophila dopaminergic cells using regulatory sequences from tyrosine hydroxylase

Wiley - Tập 54 Số 4 - Trang 618-627 - 2003
Florence Friggi‐Grelin1, Hélène Coulom1, Margaret Meller2, Delphine Gomez1, Jay Hirsh2, Serge Birman1
1Laboratoire de Génétique et Physiologie du Développement, CNRS‐Université de la Méditerranée, Developmental Biology Institute of Marseille, Campus de Luminy, Case 907, F‐13288 Marseille Cedex 9, France
2Department of Biology, University of Virginia, Gilmer Hall, Charlottesville, Virginia, 22903

Tóm tắt

AbstractDopamine (DA) is the only catecholaminergic neurotransmitter in the fruit fly Drosophila melanogaster. Dopaminergic neurons have been identified in the larval and adult central nervous system (CNS) in Drosophila and other insects, but no specific genetic tool was available to study their development, function, and degeneration in vivo. In Drosophila as in vertebrates, the rate‐limiting step in DA biosynthesis is catalyzed by the enzyme tyrosine hydroxylase (TH). The Drosophila TH gene (DTH) is specifically expressed in all dopaminergic cells and the corresponding mutant, pale (ple), is embryonic lethal. We have performed ple rescue experiments with modified DTH transgenes. Our results indicate that partially redundant regulatory elements located in DTH introns are required for proper expression of this gene in the CNS. Based on this study, we generated a GAL4 driver transgene, TH‐GAL4, containing regulatory sequences from the DTH 5′ flanking and downstream coding regions. TH‐GAL4 specifically expresses in dopaminergic cells in embryos, larval CNS, and adult brain when introduced into the Drosophila genome. As a first application of this driver, we observed that in vivo inhibition of DA release induces a striking hyperexcitability behavior in adult flies. We propose that TH‐GAL4 will be useful for studies of the role of DA in behavior and disease models in Drosophila. © 2003 Wiley Periodicals, Inc. J Neurobiol 54: 618–627, 2003

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Tài liệu tham khảo

10.1073/pnas.97.4.1873

10.1126/science.1067389

10.1038/377424a0

10.1016/S0960-9822(00)00336-5

10.1101/gad.1.5.510

10.1016/S0021-9258(18)47231-6

10.1242/dev.118.2.401

10.1523/JNEUROSCI.06-12-03682.1986

10.3109/01677068709102351

10.1002/cne.902680309

10.1002/neu.480170102

10.1006/exnr.1996.6379

10.1016/S0065-2806(08)60143-5

10.1038/35006074

10.1093/nar/27.1.85

10.1002/gene.10178

10.1016/0531-5565(78)90012-8

10.1038/379606a0

10.1007/BF00217108

10.1007/BF00848157

10.1016/0092-8674(84)90534-8

10.1046/j.1471-4159.1996.67020443.x

10.1016/S0960-9822(00)00340-7

10.1006/dbio.1994.1261

10.1016/S0960-9822(98)70041-7

10.1037/0735-7044.113.4.744

10.1002/(SICI)1097-0029(19990415)45:2<106::AID-JEMT5>3.0.CO;2-3

10.1016/0301-0082(95)00048-8

10.1007/BF00318701

10.1002/neu.1035

10.3109/01677069809167259

10.1016/0896-6273(89)90183-9

10.3109/01677069309083448

10.1016/0022-1910(90)90028-E

Pirrotta V, 1988, Vectors. A survey of molecular cloning vectors and their uses, 437

Restifo LL, 1990, Molecular and genetic approaches to neurotransmitter and neuromodulator systems in Drosophila, Adv Insect Phys, 22, 116

10.1126/science.6289436

10.1016/S0166-4328(01)00431-4

10.1016/0896-6273(95)90290-2

10.1007/BF00291041

10.1073/pnas.81.11.3577

10.1007/BF00217165

10.1074/jbc.274.24.16788

10.1016/S0065-2660(08)60008-5

10.1073/pnas.94.8.4131

10.1016/0092-8674(95)90145-0

10.1146/annurev.ne.12.030189.002215

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Wiley

Tập 54 Số 4

618-627

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