title: Transcriptional control of steroid biosynthesis genes in the Drosophila prothoracic gland by ventral veins lacking and knirps.
abstract: Specialized endocrine cells produce and release steroid hormones that govern development, metabolism and reproduction. In order to synthesize steroids, all the genes in the biosynthetic pathway must be coordinately turned on in steroidogenic cells. In Drosophila, the steroid producing endocrine cells are located in the prothoracic gland (PG) that releases the steroid hormone ecdysone. The transcriptional regulatory network that specifies the unique PG specific expression pattern of the ecdysone biosynthetic genes remains unknown. Here, we show that two transcription factors, the POU-domain Ventral veins lacking (Vvl) and the nuclear receptor Knirps (Kni), have essential roles in the PG during larval development. Vvl is highly expressed in the PG during embryogenesis and is enriched in the gland during larval development, suggesting that Vvl might function as a master transcriptional regulator in this tissue. Vvl and Kni bind to PG specific cis-regulatory elements that are required for expression of the ecdysone biosynthetic genes. Knock down of either vvl or kni in the PG results in a larval developmental arrest due to failure in ecdysone production. Furthermore, Vvl and Kni are also required for maintenance of TOR/S6K and prothoracicotropic hormone (PTTH) signaling in the PG, two major pathways that control ecdysone biosynthesis and PG cell growth. We also show that the transcriptional regulator, Molting defective (Mld), controls early biosynthetic pathway steps. Our data show that Vvl and Kni directly regulate ecdysone biosynthesis by transcriptional control of biosynthetic gene expression and indirectly by affecting PTTH and TOR/S6K signaling. This provides new insight into the regulatory network of transcription factors involved in the coordinated regulation of steroidogenic cell specific transcription, and identifies a new function of Vvl and Knirps in endocrine cells during post-embryonic development.
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: E Thomas
authors.initials: ET
authors.lastname: Danielsen
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Morten E
authors.initials: ME
authors.lastname: Moeller
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Elad
authors.initials: E
authors.lastname: Dorry
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Komura-Kawa
authors.affiliation: Department of Chemistry and Materials Science, Tokyo Institute of Technology, Meguro, Tokyo, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fujimoto
authors.affiliation: Department of Science, Systems and Models, Roskilde University, Roskilde, Denmark.
authors.forename: Jesper T
authors.initials: JT
authors.lastname: Troelsen
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Rachel
authors.initials: R
authors.lastname: Herder
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Michael B
authors.initials: MB
authors.lastname: O'Connor
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan; PRESTO, JST, Kawaguchi, Saitama, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Niwa
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kim F
authors.initials: KF
authors.lastname: Rewitz
mesh_terms: D000818:Animals; D001665:Binding Sites; D001692:Biological Transport / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics; D004440:Ecdysone / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D007301:Insect Hormones / Q000096:biosynthesis* / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis; D009687:Nuclear Proteins / Q000378:metabolism*; D050809:POU Domain Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000096:biosynthesis*; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D007301:Insect Hormones; C500751:MLD protein, Drosophila; D008565:Membrane Proteins; D009687:Nuclear Proteins; D050809:POU Domain Factors; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C074089:kni protein, Drosophila; C091575:vvl protein, Drosophila; D004440:Ecdysone; C009089:prothoracicotropic hormone; D002784:Cholesterol; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases