1. Cell Biology
  2. Developmental Biology

The NDNF-like factor Nord is a Hedgehog-induced extracellular BMP modulator that regulates Drosophila wing patterning and growth

  1. Shu Yang
  2. Xuefeng Wu
  3. Euphrosyne I Daoutidou
  4. Ya Zhang
  5. MaryJane Shimell
  6. Kun-Han Chuang
  7. Aidan J Peterson
  8. Michael B O'Connor
  9. Xiaoyan Zheng  Is a corresponding author
  1. George Washington University, United States
  2. University of Minnesota, United States
https://doi.org/10.7554/eLife.73357
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  1. Shu Yang
  2. Xuefeng Wu
  3. Euphrosyne I Daoutidou
  4. Ya Zhang
  5. MaryJane Shimell
  6. Kun-Han Chuang
  7. Aidan J Peterson
  8. Michael B O'Connor
  9. Xiaoyan Zheng
(2022)
The NDNF-like factor Nord is a Hedgehog-induced extracellular BMP modulator that regulates Drosophila wing patterning and growth
eLife 11:e73357.
https://doi.org/10.7554/eLife.73357
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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-depend 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.

Data availability

The raw microarray data were deposited to the Gene Expression Omnibus public repository (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE180120; Gene Expression Omnibus series no. GSE180120).

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Shu Yang

    Department of Anatomy and Cell Biology, George Washington University, Washington, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Xuefeng Wu

    Department of Anatomy and Cell Biology, George Washington University, Washington, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Euphrosyne I Daoutidou

    Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Ya Zhang

    Department of Anatomy and Cell Biology, George Washington University, Washington, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9060-3777

  5. MaryJane Shimell

    Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Kun-Han Chuang

    Department of Anatomy and Cell Biology, George Washington University, Washington, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3241-8586

  7. Aidan J Peterson

    Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6801-3364

  8. Michael B O'Connor

    Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3067-5506

  9. Xiaoyan Zheng

    Department of Anatomy and Cell Biology, George Washington University, Washington, United States
    For correspondence
    xzheng@gwu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4983-5503

Funding

NIGMS (R01GM117440)

  • Xiaoyan Zheng

NIGMS (R35GM118029)

  • Michael B O'Connor

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2022, Yang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Shu Yang
  2. Xuefeng Wu
  3. Euphrosyne I Daoutidou
  4. Ya Zhang
  5. MaryJane Shimell
  6. Kun-Han Chuang
  7. Aidan J Peterson
  8. Michael B O'Connor
  9. Xiaoyan Zheng
(2022)
The NDNF-like factor Nord is a Hedgehog-induced extracellular BMP modulator that regulates Drosophila wing patterning and growth
eLife 11:e73357.
https://doi.org/10.7554/eLife.73357

Share this article

https://doi.org/10.7554/eLife.73357

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