Sulfated is a negative feedback regulator of wingless in Drosophila

Authors

  • Jia You,

    1. Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, and The Graduate Program in Molecular and Developmental Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio
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  • Tatyana Belenkaya,

    1. Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, and The Graduate Program in Molecular and Developmental Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio
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  • Xinhua Lin

    Corresponding author
    1. Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, and The Graduate Program in Molecular and Developmental Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio
    2. State key Laboratory of Biomembrane and Membrane Biotechnology, and Key Laboratory of Stem Cell and Developmental Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    • Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229
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Abstract

Drosophila Wingless (Wg) acts as a morphogen to control pattern formation in a concentration dependent manner. Previous studies demonstrated important roles of heparan sulfate proteoglycans (HSPGs) in controlling Wg signaling and distribution. Here, we examined the role of Sulfated (Sulf1), a Drosophila homolog of vertebrate heparan sulfate 6-O endosulfatase, in Wg signaling and distribution. We show that sulf1 is specifically up-regulated by Wg signaling in the wing disc. We found that expression of Wg target gene senseless (sens) was elevated in the sulf1 mutant wing discs. Sulf1 also negatively regulate extracellular levels of Wg. Genetic interaction experiments indicate that Wg antagonist Notum may work synergistically with Sulf1 to restrict Wg signaling, and Dally, a member of Drosophila HSPGs, is a potential target of Sulf1. Our results demonstrate that sulf1 is a novel Wg target gene and by a feedback mechanism, it negatively regulated Wg signaling and distribution in vivo. Developmental Dynamics 240:640–648, 2011. © 2011 Wiley-Liss, Inc.

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