title: BMP-dependent gene repression cascade in Drosophila eggshell patterning.
abstract: Bone Morphogenetic Proteins (BMPs) signal by activating Smad transcription factors to control a number of decisions during animal development. In Drosophila, signaling by the BMP ligand Decapentaplegic (Dpp) involves the activity of brinker (brk) which, in most contexts, is repressed by Dpp. Brk encodes a transcription factor which represses BMP signaling output by antagonizing Smad-dependent target gene activation. Here, we study BMP-dependent gene regulation during Drosophila oogenesis by following the signal transmission from Dpp to its target broad (br), a gene with a crucial function in eggshell patterning. We identify regulatory sequences that account for expression of both brk and br, and connect these to the transcription factors of the pathway. We show that Dpp directly regulates brk transcription through Smad- and Schnurri (Shn)-dependent repression. Brk is epistatic to Dpp in br expression and activates br indirectly, through removal of a repressor, which is yet to be identified. Our work provides first cis-regulatory insights into transcriptional interpretation of BMP signaling in eggshell morphogenesis and defines a transcriptional cascade that connects Dpp to target gene regulation.
authors.affiliation: Institute for Biology I, Faculty of Biology, Albert-Ludwigs-University of Freiburg, Germany; Research Training Program GRK 1104, Albert-Ludwigs-University of Freiburg, Germany; BIOSS Centre for Biological Signaling Studies, Albert-Ludwigs-University of Freiburg, Schänzlestr. 18, 79104 Freiburg, Germany.
authors.forename: Enrica
authors.initials: E
authors.lastname: Charbonnier
authors.affiliation: Institute for Biology I, Faculty of Biology, Albert-Ludwigs-University of Freiburg, Germany.
authors.forename: Alisa
authors.initials: A
authors.lastname: Fuchs
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Lily S
authors.initials: LS
authors.lastname: Cheung
authors.affiliation: Research Training Program GRK 1104, Albert-Ludwigs-University of Freiburg, Germany; BIOSS Centre for Biological Signaling Studies, Albert-Ludwigs-University of Freiburg, Schänzlestr. 18, 79104 Freiburg, Germany.
authors.forename: Mrinal
authors.initials: M
authors.lastname: Chayengia
authors.affiliation: BIOSS Centre for Biological Signaling Studies, Albert-Ludwigs-University of Freiburg, Schänzlestr. 18, 79104 Freiburg, Germany.
authors.forename: Ville
authors.initials: V
authors.lastname: Veikkolainen
authors.affiliation: Institute for Biology I, Faculty of Biology, Albert-Ludwigs-University of Freiburg, Germany; BIOSS Centre for Biological Signaling Studies, Albert-Ludwigs-University of Freiburg, Schänzlestr. 18, 79104 Freiburg, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Seyfferth
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Stanislav Y
authors.initials: SY
authors.lastname: Shvartsman
authors.affiliation: Institute for Biology I, Faculty of Biology, Albert-Ludwigs-University of Freiburg, Germany; BIOSS Centre for Biological Signaling Studies, Albert-Ludwigs-University of Freiburg, Schänzlestr. 18, 79104 Freiburg, Germany. Electronic address: g.pyrowolakis@biologie.uni-freiburg.de.
authors.forename: George
authors.initials: G
authors.lastname: Pyrowolakis
mesh_terms: D000818:Animals; D019521:Body Patterning; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D009866:Oogenesis; D006080:Ovarian Follicle / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D012097:Repressor Proteins; C118082:brk protein, Drosophila; C064196:dpp protein, Drosophila
keywords: BMP signaling; Brinker; Broad; Dpp; Drosophila; Oogenesis