1. Department of Organismal Biology and Anatomy and
2. Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, Illinois 60637, USA

Correspondence to: Edwin L. Ferguson^1,2 Correspondence and requests for materials should be addressed E.L.F. (Email: elfergus@midway.uchicago.edu).

Abstract

In many developmental contexts, a locally produced morphogen specifies positional information by forming a concentration gradient over a field of cells¹. 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^{2, 3, 4}. 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.

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