PT  - JOURNAL ARTICLE
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
TI  - The NDNF-like factor Nord is a Hedgehog-induced extracellular BMP modulator that regulates <em>Drosophila</em> wing patterning and growth
AID  - 10.1101/2021.09.06.459106
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.09.06.459106
4099  - http://biorxiv.org/content/early/2021/09/06/2021.09.06.459106.short
4100  - http://biorxiv.org/content/early/2021/09/06/2021.09.06.459106.full
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-depend biphasic 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.One sentence summary The NDNF-like factor Nord is a Hedgehog-induced and extracellular-localized biphasic BMP modulator that regulates Drosophila wing patterning and growthCompeting Interest StatementThe authors have declared no competing interest.