RRC ID 70787
著者 Yang S, Wu X, Daoutidou EI, Zhang Y, Shimell M, Chuang KH, Peterson AJ, O'Connor MB, Zheng X.
タイトル The NDNF-like factor Nord is a Hedgehog-induced extracellular BMP modulator that regulates Drosophila wing patterning and growth.
ジャーナル Elife
Abstract 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.
巻・号 11
公開日 2022-1-17
DOI 10.7554/eLife.73357
PII 73357
PMID 35037619
PMC PMC8856659
MeSH Animals Body Patterning / genetics Body Patterning / physiology* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / growth & development* Gene Expression Regulation, Developmental / physiology* Hedgehog Proteins / genetics Hedgehog Proteins / metabolism* Larva / growth & development Larva / metabolism Wings, Animal / growth & development*
IF 7.08
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