TY - JOUR TI - The NDNF-like factor Nord is a Hedgehog-induced extracellular BMP modulator that regulates Drosophila wing patterning and growth AU - Yang, Shu AU - Wu, Xuefeng AU - Daoutidou, Euphrosyne I AU - Zhang, Ya AU - Shimell, MaryJane AU - Chuang, Kun-Han AU - Peterson, Aidan J AU - O'Connor, Michael B AU - Zheng, Xiaoyan A2 - Bach, Erika A A2 - Banerjee, Utpal A2 - Bach, Erika A VL - 11 PY - 2022 DA - 2022/01/17 SP - e73357 C1 - eLife 2022;11:e73357 DO - 10.7554/eLife.73357 UR - https://doi.org/10.7554/eLife.73357 AB - Hedgehog (Hh) and Bone Morphogenetic Proteins (BMPs) pattern the developing Drosophila wing by functioning as short- and long-range morphogens, respectively. Here, we show that a previously unknown Hh-dependent mechanism fine-tunes the activity of BMPs. Through genome-wide expression profiling of the Drosophila wing imaginal discs, we identify nord as a novel target gene of the Hh signaling pathway. Nord is related to the vertebrate Neuron-Derived Neurotrophic Factor (NDNF) involved in congenital hypogonadotropic hypogonadism and several types of cancer. Loss- and gain-of-function analyses implicate Nord in the regulation of wing growth and proper crossvein patterning. At the molecular level, we present biochemical evidence that Nord is a secreted BMP-binding protein and localizes to the extracellular matrix. Nord binds to Decapentaplegic (Dpp) or the heterodimer Dpp-Glass-bottom boat (Gbb) to modulate their release and activity. Furthermore, we demonstrate that Nord is a dosage-dependent BMP modulator, where low levels of Nord promote and high levels inhibit BMP signaling. Taken together, we propose that Hh-induced Nord expression fine-tunes both the range and strength of BMP signaling in the developing Drosophila wing. KW - signal transduction KW - Hedgehog KW - BMP KW - patterning KW - growth KW - biphasic modulator JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -