A Novel Role for UDP-GlcNAC in Dpp Signal Antagonism. Matthew J. Moulton, Gregory Humphreys, Anthea Letsou. Human Genetics, University of Utah, Salt Lake City, UT.

   mummy (mmy), a member of the raw group of signaling antagonists, encodes the single Drosophila UDP-N-acetylglucosamine pyrophosphorylase. Mmys effects on signal antagonism are most evident in the context of embryonic dorsal closure. In this developmental context, the JNK/AP-1 signaling cascade transcriptionally activates Dpp signaling in leading edge (LE) epidermal cells. Whereas dpp expression is confined to LE cells in wild-type embryos, it expands ectopically into the dorsolateral epidermis in mmy mutant embryos, establishing Mmy as a dpp antagonist. To identify downstream effectors of Dpp signal restriction, we screened the 25 Drosophila glycosyltransferases potentially utilizing UDP-GlcNAc downstream of Mmy. Embryos depleted of several of these transferases phenocopy mmy loss-of-function phenotypes. In at least one case, transferase depletion leads to dpp expresson beyond the LE in the epidermis. These data suggest a role for GlcNAc modifications that is critical to development and the control of signaling.