title: Autoregulation of the Drosophila disconnected gene in the developing visual system.
abstract: The Drosophila disconnected (disco) gene is required for the formation of appropriate connections between the larval optic nerve and its target cells in the brain. The disco gene encodes a nuclear protein with two zinc fingers, which suggests that the gene product is a transcription factor. Here, we present data supporting this notion. We find that disco expression in the optic lobe primordium, a group of cells contacted by the developing optic nerve, depends on an autoregulatory feedback loop. We show that wild-type disco function is required for maintenance of disco mRNA and protein expression in the developing optic lobe. In addition, we demonstrate that ubiquitous Disco activity supplied by a heat-inducible gene construct activates expression from the endogenous disco gene specifically in the optic lobe primordium. Consistent with a role of Disco as a transcriptional regulatory protein, we show that portions of the Disco protein are capable of activating the transcription of reporter constructs in a heterologous system. Moreover, we find that the zinc finger portion of Disco binds in vitro to sequences located near the disco transcription unit, suggesting that Disco autoregulates its transcription in the optic lobe primordium by direct binding to a regulatory element in its own promoter.
authors.affiliation: Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Mukhopadhyay
authors.forename: P
authors.initials: P
authors.lastname: Pelka
authors.forename: A R
authors.initials: AR
authors.lastname: Campos
authors.forename: H
authors.initials: H
authors.lastname: Steller
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D017930:Genes, Reporter; D006706:Homeostasis; D017403:In Situ Hybridization; D007814:Larva / Q000254:growth & development; D008957:Models, Genetic; D009899:Optic Lobe, Nonmammalian / Q000196:embryology; D017956:Photoreceptor Cells, Invertebrate / Q000196:embryology*; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D000099160:LexA Repressor Protein
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012697:Serine Endopeptidases; D014157:Transcription Factors; D000099160:LexA Repressor Protein; C400212:disco protein, Drosophila