Response to the BMP gradient requires highly combinatorial inputs from multiple patterning systems in the Drosophila embryo

Development. 2012 Jun;139(11):1956-64. doi: 10.1242/dev.079772. Epub 2012 Apr 18.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binding Sites / genetics
  • Body Patterning / physiology*
  • Drosophila / embryology*
  • Drosophila / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Electrophoresis, Polyacrylamide Gel
  • Enhancer Elements, Genetic / genetics
  • Gene Expression Regulation, Developmental / physiology*
  • In Situ Hybridization
  • Mutagenesis
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / metabolism
  • Smad Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Drosophila Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Smad Proteins
  • Transcription Factors
  • brk protein, Drosophila
  • dpp protein, Drosophila
  • pnr protein, Drosophila