title: Smad affinity can direct distinct readouts of the embryonic extracellular Dpp gradient in Drosophila.
abstract: BACKGROUND
  The TGF-beta signaling molecule Decapentaplegic (Dpp) is an essential morphogen that patterns many tissues during Drosophila development, including the embryonic dorsal ectoderm and larval wing imaginal disk. An activity gradient of Dpp specifies distinct cell fates in the dorsal ectoderm of the embryo through the activation of different transcriptional threshold responses.
  
  
  RESULTS
  We have analyzed the gene Race, which is expressed in response to peak levels of Dpp signaling in gastrulating embryos. We show that the Smad transcription factors, which are intracellular transducers of Dpp signaling, are essential activators of Race in vivo. Furthermore, increasing the affinity of the Smad binding sites in the Race enhancer broadens the expression pattern of a linked reporter gene and alters its behavior in mutant embryos to that characteristic of a distinct threshold response.
  
  
  CONCLUSIONS
  Smad activator affinity is a critical determinant of the threshold response to the extracellular Dpp gradient in the embryo. Our results identify a mechanism for interpreting the Dpp gradient in the embryo which is different to the reciprocal repressor gradient model proposed for the wing disk. We suggest that transcription factor binding site affinity will be a general strategy used in the interpretation of other extracellular morphogen gradients.
authors.affiliation: School of Biological Sciences, University of Manchester, Manchester, M13 9PT, United Kingdom.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Wharton
authors.forename: Sanjay P
authors.initials: SP
authors.lastname: Basu
authors.forename: Hilary L
authors.initials: HL
authors.lastname: Ashe
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology*; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005775:Gastrula / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008954:Models, Biological; D008969:Molecular Sequence Data; D009841:Oligonucleotides; D010957:Plasmids / Q000235:genetics; D023302:Protein Footprinting; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D009841:Oligonucleotides; D014157:Transcription Factors; C064196:dpp protein, Drosophila