Sonic hedgehog signaling directs patterned cell remodeling during cranial neural tube closure

  1. Eric R Brooks
  2. Mohammed Tarek Islam
  3. Kathryn V Anderson
  4. Jennifer A Zallen  Is a corresponding author
  1. Sloan Kettering Institute, United States

Abstract

Neural tube closure defects are a major cause of infant mortality, with exencephaly accounting for nearly one-third of cases. However, the mechanisms of cranial neural tube closure are not well understood. Here we show that this process involves a tissue-wide pattern of apical constriction controlled by Sonic hedgehog (Shh) signaling. Midline cells in the mouse midbrain neuroepithelium are short with large apical surfaces, whereas lateral cells are taller and undergo synchronous apical constriction, driving neural fold elevation. Embryos lacking the Shh effector Gli2 fail to produce appropriate midline cell architecture, whereas embryos with expanded Shh signaling, including the IFT-A complex mutants Ift122 and Ttc21b and embryos expressing activated Smoothened, display apical constriction defects in lateral cells. Disruption of lateral, but not midline, cell remodeling results in exencephaly. These results reveal a morphogenetic program of patterned apical constriction governed by Shh signaling that generates structural changes in the developing mammalian brain.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Eric R Brooks

    Developmental Biology Program, Sloan Kettering Institute, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3159-8626
  2. Mohammed Tarek Islam

    Developmental Biology Program, Sloan Kettering Institute, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Kathryn V Anderson

    Developmental Biology Program, Sloan Kettering Institute, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jennifer A Zallen

    Developmental Biology Program, Sloan Kettering Institute, New York, United States
    For correspondence
    zallenj@mskcc.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3975-1568

Funding

Howard Hughes Medical Institute

  • Jennifer A Zallen

National Institutes of Health (F32 NS098832)

  • Eric R Brooks

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 experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and an approved Institutional Animal Care and Use Committee protocol (15-08-13) of Memorial Sloan Kettering Cancer Center.

Reviewing Editor

  1. Jeremy F Reiter, University of California, San Francisco, United States

Publication history

  1. Received: June 20, 2020
  2. Accepted: October 25, 2020
  3. Accepted Manuscript published: October 26, 2020 (version 1)
  4. Version of Record published: November 10, 2020 (version 2)

Copyright

© 2020, Brooks 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. Eric R Brooks
  2. Mohammed Tarek Islam
  3. Kathryn V Anderson
  4. Jennifer A Zallen
(2020)
Sonic hedgehog signaling directs patterned cell remodeling during cranial neural tube closure
eLife 9:e60234.
https://doi.org/10.7554/eLife.60234
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