The NDNF-like factor Nord is a Hedgehog-induced extracellular BMP modulator that regulates wing patterning and growth
BMP; D. melanogaster; Hedgehog; biphasic modulator; cell biology; developmental biology; growth; patterning; signal transduction
Hedgehog (Hh) and Bone Morphogenetic Proteins (BMPs) pattern the developing 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 wing imaginal discs, we identify 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 wing.
Yang, Shu; Wu, Xuefeng; Daoutidou, Euphrosyne I.; Zhang, Ya; Shimell, MaryJane; Chuang, Kun-Han; Peterson, Aidan J.; O'Connor, Michael B.; and Zheng, Xiaoyan, "The NDNF-like factor Nord is a Hedgehog-induced extracellular BMP modulator that regulates wing patterning and growth" (2022). GW Authored Works. Paper 255.
Anatomy and Regenerative Biology