Local inhibition and long-range enhancement of Dpp signal transduction by Sog

Hilary L. Ashe and Michael Levine ()
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Hilary L. Ashe: 401 Barker Hall, University of California
Michael Levine: 401 Barker Hall, University of California

Nature, 1999, vol. 398, issue 6726, 427-431

Abstract: Abstract Extracellular gradients of signalling molecules can specify different thresholds of gene activity in development. A gradient of Decapentaplegic (Dpp) activity subdivides the dorsal ectoderm of the Drosophila embryo into amnioserosa and dorsal epidermis1,2. The proteins Short gastrulation3 (Sog) and Tolloid4 (Tld) are required to shape this gradient. Sog has been proposed to form an inhibitory complex with either Dpp5 or the related ligand Screw6,7, and is subsequently processed by the protease Tld5. Paradoxically, Sog appears to be required for amnioserosa formation8, which is specified by peak Dpp signalling activity1,2. Here we show that the misexpression of sog using the even-skipped stripe-2 enhancer9 redistributes Dpp signalling in a mutant background in which dpp is expressed throughout the embryo. Dpp activity is diminished near the Sog stripe and peak Dpp signalling is detected far from this stripe. However, a tethered form of Sog suppresses local Dpp activity without augmenting Dpp activity at a distance, indicating that diffusion of Sog may be required for enhanced Dpp activity and consequent amnioserosa formation. The long-distance stimulation of Dpp activity by Sog requires Tld, whereas Sog-mediated inhibition of Dpp does not. The heterologous Dpp inhibitor Noggin10 inhibits Dpp signalling but fails to augment Dpp activity. These results suggest an unusual strategy for generating a gradient threshold of growth-factor activity, whereby Sog and its protease specify peak Dpp signalling far from a localized source of Sog.

Date: 1999
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DOI: 10.1038/18892

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