1. Developmental Biology
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Mutations associated with human neural tube defects display disrupted planar cell polarity in Drosophila

  1. Ashley C Humphries
  2. Sonali Narang
  3. Marek Mlodzik  Is a corresponding author
  1. Icahn Medical School - Mount Sinai Hospital, United States
  2. NYU School of Medicine, United States
Research Article
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Cite this article as: eLife 2020;9:e53532 doi: 10.7554/eLife.53532


Planar cell polarity (PCP) and neural tube defects (NTDs) are linked, with a subset of NTD patients found to harbour mutations in PCP genes, but there is limited data on whether these mutations disrupt PCP signaling in vivo. The core PCP gene Van Gogh (Vang), Vangl1/2 in mammals, is the most specific for PCP. We thus addressed potential causality of NTD-associated Vangl1/2 mutations, from either mouse or human patients, in Drosophila allowing intricate analysis of the PCP pathway. Introducing the respective mammalian mutations into Drosophila Vang revealed defective phenotypic and functional behaviors, with changes to Vang localization, post-translational modification, and mechanistic function, such as its ability to interact with PCP effectors. Our findings provide mechanistic insight into how different mammalian mutations contribute to developmental disorders and strengthen the link between PCP and NTD. Importantly, analyses of the human mutations revealed that each is a causative factor for the associated NTD.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2 and 5.

Article and author information

Author details

  1. Ashley C Humphries

    Cell, Developmental, and Regenerative Biology, Icahn Medical School - Mount Sinai Hospital, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Sonali Narang

    Pathology, NYU School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Marek Mlodzik

    Cell, Developmental, and Regenerative Biology, Icahn Medical School - Mount Sinai Hospital, New York, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0628-3465


National Institute of General Medical Sciences (R35 GM127103)

  • Marek Mlodzik

National Eye Institute (R01 EY013256)

  • Marek Mlodzik

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

Reviewing Editor

  1. Hugo J Bellen, Baylor College of Medicine, United States

Publication history

  1. Received: November 12, 2019
  2. Accepted: March 31, 2020
  3. Accepted Manuscript published: April 1, 2020 (version 1)
  4. Version of Record published: April 23, 2020 (version 2)


© 2020, Humphries 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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