Genetic studies in Drosophila have revealed a novel secreted antagonist for Wingless (Wg) signaling, referred to as Notum/Wingful (Wf). Wf/Notum encodes a protein of 430 amino acid residues, which is related to plant pectin acetylesterases of the / -hydrolase superfamily. The main target of Notum action appears to be cell surface proteoglycans Dally and/or Dally-like (Dlp). Notum governs the extracellular Wg morphogen distribution via Dally and Dlp. Also, like some vertebrate Wnt antagonists, notum expression is activated by Wg signaling, revealing the existence of a feedback control mechanism in which Wg modifies its own gradient distribution. In vertebrate, proteoglycans related to Dally and Dlp likely play important roles in Wnt signaling which encodes a glypican that is required for Wnt-11 signaling. A single ortholog of Notum exists in the mouse and the human genome, implying that a similar regulatory mechanism may exist in vertebrates.
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