1. Developmental Biology
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Primary cilia deficiency in neural crest cells models Anterior Segment Dysgenesis in mouse

  1. Céline Portal
  2. Panteleimos Rompolas
  3. Peter Lwigale
  4. Carlo Iomini  Is a corresponding author
  1. Johns Hopkins University School of Medicine, United States
  2. Perelman School of Medicine, University of Pennsylvania, United States
  3. Rice University, United States
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Cite this article as: eLife 2019;8:e52423 doi: 10.7554/eLife.52423

Abstract

Defects affecting tissues of the anterior segment (AS) of the eye lead to a group of highly debilitating disorders called Anterior Segment Dysgenesis (ASD). Despite the identification of some causative genes, the pathogenesis of ASD remains unclear. Interestingly, several ciliopathies display conditions of the AS. Using conditional targeting of Ift88 with Wnt1-Cre, we show that primary cilia of neural crest cells (NCC), precursors of most AS structures, are indispensable for normal AS development and their ablation leads to ASD conditions including abnormal corneal dimensions, defective iridocorneal angle, reduced anterior chamber volume and corneal neovascularization. Mechanistically, NCC cilia ablation abolishes hedgehog (Hh) signaling in the periocular mesenchyme (POM) canonically activated by choroid-secreted Indian Hh, reduces proliferation of POM cells surrounding the retinal pigment epithelium and decreases the expression of Foxc1 and Pitx2, two transcription factors identified as major ASD causative genes. Thus, we uncovered a signaling axis linking cilia and ASD.

Article and author information

Author details

  1. Céline Portal

    Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Panteleimos Rompolas

    Department of Dermatology, Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Peter Lwigale

    BioSciences Department, Rice University, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1799-4905
  4. Carlo Iomini

    Department of Ophthalmology, Wilmer Eye Institute; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, United States
    For correspondence
    ciomini1@jhmi.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6483-9540

Funding

NIH Office of the Director (EY022639)

  • Carlo Iomini

NIH Office of the Director (EY022158)

  • Peter Lwigale

NIH Office of the Director (EY030599)

  • Panteleimos Rompolas

Research to Prevent Blindness (Dolly Green Special Scholar Award)

  • Carlo Iomini

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

Ethics

Animal experimentation: All animal procedures were performed in accordance with the guidelines and approval of the Institutional Animal Care and Use Committee at Icahn School of Medicine at Mount Sinai (protocol number: 18-1561), at Johns Hopkins University (protocol number: MO19M122), and at the University of Pennsylvania (protocol number: 805830).

Reviewing Editor

  1. Joseph G Gleeson, Howard Hughes Medical Institute, The Rockefeller University, United States

Publication history

  1. Received: October 3, 2019
  2. Accepted: December 17, 2019
  3. Accepted Manuscript published: December 17, 2019 (version 1)
  4. Version of Record published: January 7, 2020 (version 2)

Copyright

© 2019, Portal 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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