1. Developmental Biology
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Tissue-specific regulation of BMP signaling by Drosophila N-glycanase 1

  1. Antonio Galeone
  2. Seung Yeop Han
  3. Chengcheng Huang
  4. Akira Hosomi
  5. Tadashi Suzuki
  6. Hamed Jafar-Nejad  Is a corresponding author
  1. Baylor College of Medicine, United States
  2. RIKEN Global Research Cluster, Japan
Research Article
  • Cited 15
  • Views 2,429
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Cite this article as: eLife 2017;6:e27612 doi: 10.7554/eLife.27612

Abstract

Mutations in the human N-glycanase 1 (NGLY1) cause a rare, multisystem congenital disorder with global developmental delay. However, the mechanisms by which NGLY1 and its homologs regulate embryonic development are not known. Here we show that Drosophila Pngl encodes an N-glycanase and exhibits a high degree of functional conservation with human NGLY1. Loss of Pngl results in developmental midgut defects reminiscent of midgut-specific loss of BMP signaling. Pngl mutant larvae also exhibit a severe midgut clearance defect, which cannot be fully explained by impaired BMP signaling. Genetic experiments indicate that Pngl is primarily required in the mesoderm during Drosophila development. Loss of Pngl results in a severe decrease in the level of Dpp homodimers and abolishes BMP autoregulation in the visceral mesoderm mediated by Dpp and Tkv homodimers. Thus, our studies uncover a novel mechanism for the tissue-specific regulation of an evolutionarily conserved signaling pathway by an N-glycanase enzyme.

Article and author information

Author details

  1. Antonio Galeone

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Seung Yeop Han

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Chengcheng Huang

    Glycometabolome Team, RIKEN Global Research Cluster, Saitama, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Akira Hosomi

    Glycometabolome Team, RIKEN Global Research Cluster, Saitama, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Tadashi Suzuki

    Glycometabolome Team, RIKEN Global Research Cluster, Saitama, Japan
    Competing interests
    The authors declare that no competing interests exist.
  6. Hamed Jafar-Nejad

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    For correspondence
    hamedj@bcm.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6403-3379

Funding

Grace Wilsey Foundation (Research Grant)

  • Tadashi Suzuki
  • Hamed Jafar-Nejad

National Institutes of Health (R01GM084135 R01DK109982)

  • Hamed Jafar-Nejad

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

Reviewing Editor

  1. K VijayRaghavan, National Centre for Biological Sciences, Tata Institute of Fundamental Research, India

Publication history

  1. Received: April 8, 2017
  2. Accepted: August 3, 2017
  3. Accepted Manuscript published: August 4, 2017 (version 1)
  4. Version of Record published: September 14, 2017 (version 2)

Copyright

© 2017, Galeone 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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