Spatial bistability of Dpp-receptor interactions during Drosophila dorsal-ventral patterning

Nature. 2005 Mar 10;434(7030):229-34. doi: 10.1038/nature03318.

Abstract

In many developmental contexts, a locally produced morphogen specifies positional information by forming a concentration gradient over a field of cells. However, during embryonic dorsal-ventral patterning in Drosophila, two members of the bone morphogenetic protein (BMP) family, Decapentaplegic (Dpp) and Screw (Scw), are broadly transcribed but promote receptor-mediated signalling in a restricted subset of expressing cells. Here we use a novel immunostaining protocol to visualize receptor-bound BMPs and show that both proteins become localized to a sharp stripe of dorsal cells. We demonstrate that proper BMP localization involves two distinct processes. First, Dpp undergoes directed, long-range extracellular transport. Scw also undergoes long-range movement, but can do so independently of Dpp transport. Second, an intracellular positive feedback circuit promotes future ligand binding as a function of previous signalling strength. These data elicit a model in which extracellular Dpp transport initially creates a shallow gradient of BMP binding that is acted on by positive intracellular feedback to produce two stable states of BMP-receptor interactions, a spatial bistability in which BMP binding and signalling capabilities are high in dorsal-most cells and low in lateral cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Patterning / physiology*
  • Dimerization
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / metabolism*
  • Immunohistochemistry
  • Ligands
  • Protein Transport
  • Signal Transduction
  • Tolloid-Like Metalloproteinases
  • Transforming Growth Factor beta / metabolism

Substances

  • Drosophila Proteins
  • Ligands
  • SCW protein, Drosophila
  • TSG protein, Drosophila
  • Transforming Growth Factor beta
  • dpp protein, Drosophila
  • sog protein, Drosophila
  • Tolloid-Like Metalloproteinases
  • tld protein, Drosophila