title: Tools for neuroanatomy and neurogenetics in Drosophila.
abstract: We demonstrate the feasibility of generating thousands of transgenic Drosophila melanogaster lines in which the expression of an exogenous gene is reproducibly directed to distinct small subsets of cells in the adult brain. We expect the expression patterns produced by the collection of 5,000 lines that we are currently generating to encompass all neurons in the brain in a variety of intersecting patterns. Overlapping 3-kb DNA fragments from the flanking noncoding and intronic regions of genes thought to have patterned expression in the adult brain were inserted into a defined genomic location by site-specific recombination. These fragments were then assayed for their ability to function as transcriptional enhancers in conjunction with a synthetic core promoter designed to work with a wide variety of enhancer types. An analysis of 44 fragments from four genes found that >80% drive expression patterns in the brain; the observed patterns were, on average, comprised of <100 cells. Our results suggest that the D. melanogaster genome contains >50,000 enhancers and that multiple enhancers drive distinct subsets of expression of a gene in each tissue and developmental stage. We expect that these lines will be valuable tools for neuroanatomy as well as for the elucidation of neuronal circuits and information flow in the fly brain.
authors.affiliation: Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn VA 20147, USA.
authors.forename: Barret D
authors.initials: BD
authors.lastname: Pfeiffer
authors.forename: Arnim
authors.initials: A
authors.lastname: Jenett
authors.forename: Ann S
authors.initials: AS
authors.lastname: Hammonds
authors.forename: Teri-T B
authors.initials: TT
authors.lastname: Ngo
authors.forename: Sima
authors.initials: S
authors.lastname: Misra
authors.forename: Christine
authors.initials: C
authors.lastname: Murphy
authors.forename: Audra
authors.initials: A
authors.lastname: Scully
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Carlson
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Wan
authors.forename: Todd R
authors.initials: TR
authors.lastname: Laverty
authors.forename: Chris
authors.initials: C
authors.lastname: Mungall
authors.forename: Rob
authors.initials: R
authors.lastname: Svirskas
authors.forename: James T
authors.initials: JT
authors.lastname: Kadonaga
authors.forename: Chris Q
authors.initials: CQ
authors.lastname: Doe
authors.forename: Michael B
authors.initials: MB
authors.lastname: Eisen
authors.forename: Susan E
authors.initials: SE
authors.lastname: Celniker
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Rubin
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D035843:Biomedical Research / Q000379:methods; D001921:Brain / Q000166:cytology; D004331:Drosophila melanogaster; D004742:Enhancer Elements, Genetic / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D009474:Neurons / Q000378:metabolism*; D009488:Neurosciences / Q000379:methods*; D011995:Recombination, Genetic / Q000235:genetics*