title: Response to the BMP gradient requires highly combinatorial inputs from multiple patterning systems in the Drosophila embryo.
abstract: Pattern formation in the developing embryo relies on key regulatory molecules, many of which are distributed in concentration gradients. For example, a gradient of BMP specifies cell fates along the dorsoventral axis in species ranging from flies to mammals. In Drosophila, a gradient of the BMP molecule Dpp gives rise to nested domains of target gene expression in the dorsal region of the embryo; however, the mechanisms underlying the differential response are not well understood, partly owing to an insufficient number of well-studied targets. Here we analyze how the Dpp gradient regulates expression of pannier (pnr), a candidate low-level Dpp target gene. We predicted that the pnr enhancer would contain high-affinity binding sites for the Dpp effector Smad transcription factors, which would be occupied in the presence of low-level Dpp. Unexpectedly, the affinity of Smad sites in the pnr enhancer was similar to those in the Race enhancer, a high-level Dpp target gene, suggesting that the affinity threshold mechanism plays a minimal role in the regulation of pnr. Our results indicate that a mechanism involving a conserved bipartite motif that is predicted to bind a homeodomain factor in addition to Smads and the Brinker repressor, establishes the pnr expression domain. Furthermore, the pnr enhancer has a highly complex structure that integrates cues not only from the dorsoventral axis, but also from the anteroposterior and terminal patterning systems in the blastoderm embryo.
authors.affiliation: Department of Biology, Center for Developmental Genetics, New York University, New York, NY 10003, USA.
authors.forename: Hsiao-Lan
authors.initials: HL
authors.lastname: Liang
authors.forename: Mu
authors.initials: M
authors.lastname: Xu
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Chuang
authors.forename: Christine
authors.initials: C
authors.lastname: Rushlow
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D019521:Body Patterning / Q000502:physiology*; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004742:Enhancer Elements, Genetic / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D017403:In Situ Hybridization; D016296:Mutagenesis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D051785:Smad Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D051785:Smad Proteins; D014157:Transcription Factors; C118082:brk protein, Drosophila; C064196:dpp protein, Drosophila; C109259:pnr protein, Drosophila