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Cell
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Conversion of an Extracellular Dpp/BMP Morphogen Gradient into an Inverse Transcriptional Gradient

Authors: Müller, B; Hartmann, B; Pyrowolakis, G; Affolter, M; Basler, K;

Conversion of an Extracellular Dpp/BMP Morphogen Gradient into an Inverse Transcriptional Gradient

Abstract

Morphogen gradients control body pattern by differentially regulating cellular behavior. Here, we analyze the molecular events underlying the primary response to the Dpp/BMP morphogen in Drosophila. Throughout development, Dpp transduction causes the graded transcriptional downregulation of the brinker (brk) gene. We first provide significance for the brk expression gradient by showing that different Brk levels repress distinct combinations of wing genes expressed at different distances from Dpp-secreting cells. We then dissect the brk regulatory region and identify two separable elements with opposite properties, a constitutive enhancer and a Dpp morphogen-regulated silencer. Furthermore, we present genetic and biochemical evidence that the brk silencer serves as a direct target for a protein complex consisting of the Smad homologs Mad/Medea and the zinc finger protein Schnurri. Together, our results provide the molecular framework for a mechanism by which the extracellular Dpp/BMP morphogen establishes a finely tuned, graded read-out of transcriptional repression.

Countries
Germany, Switzerland
Related Organizations
Keywords

570, Macromolecular Substances, 1300 General Biochemistry, Genetics and Molecular Biology, Genes, Regulator, Silencer Elements, Transcriptional, Animals, Drosophila Proteins, Amino Acid Sequence, Body Patterning, Smad4 Protein, Biochemistry, Genetics and Molecular Biology(all), Gene Expression Regulation, Developmental, 10124 Institute of Molecular Life Sciences, DNA-Binding Proteins, Repressor Proteins, Drosophila melanogaster, Enhancer Elements, Genetic, Larva, Bone Morphogenetic Proteins, Trans-Activators, 570 Life sciences; biology, Extracellular Space, Signal Transduction, Transcription Factors

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    citations
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    158
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
158
Top 10%
Top 10%
Top 1%
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