title: Spatial bistability of Dpp-receptor interactions during Drosophila dorsal-ventral patterning.
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.
authors.affiliation: Department of Organismal Biology and Anatomy, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Yu-Chiun
authors.initials: YC
authors.lastname: Wang
authors.forename: Edwin L
authors.initials: EL
authors.lastname: Ferguson
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D019281:Dimerization; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D007150:Immunohistochemistry; D008024:Ligands; D021381:Protein Transport; D015398:Signal Transduction; D055394:Tolloid-Like Metalloproteinases; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D008024:Ligands; C090409:SCW protein, Drosophila; C090223:TSG protein, Drosophila; D016212:Transforming Growth Factor beta; C064196:dpp protein, Drosophila; C091428:sog protein, Drosophila; D055394:Tolloid-Like Metalloproteinases; C071471:tld protein, Drosophila