1. Developmental Biology
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Fgf4 maintains Hes7 levels critical for normal somite segmentation clock function

  1. Matthew J Anderson
  2. Valentin Magidson
  3. Ryoichiro Kageyama
  4. Mark Lewandoski  Is a corresponding author
  1. National Cancer Institute, National Institutes of Health, United States
  2. Frederick National Laboratory for Cancer Research, United States
  3. Kyoto University, Japan
Research Article
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Cite this article as: eLife 2020;9:e55608 doi: 10.7554/eLife.55608

Abstract

During vertebrate development, the presomitic mesoderm (PSM) periodically segments into somites, which will form the segmented vertebral column and associated muscle, connective tissue, and dermis. The periodicity of somitogenesis is regulated by a segmentation clock of oscillating Notch activity. Here, we examined mouse mutants lacking only Fgf4 or Fgf8, which we previously demonstrated act redundantly to prevent PSM differentiation. Fgf8 is not required for somitogenesis, but Fgf4 mutants display a range of vertebral defects. We analyzed Fgf4 mutants by quantifying mRNAs fluorescently labeled by hybridization chain reaction within Imaris-based volumetric tissue subsets. These data indicate that FGF4 maintains Hes7 levels and normal oscillatory patterns. To support our hypothesis that FGF4 regulates somitogenesis through Hes7, we demonstrate genetic synergy between Hes7 and Fgf4, but not with Fgf8. Our data indicate that Fgf4 is potentially important in a spectrum of human Segmentation Defects of the Vertebrae caused by defective Notch oscillations.

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. Matthew J Anderson

    Genetics of Vertebrate Development Section, Cancer and Developmental Biology Lab, National Cancer Institute, National Institutes of Health, Frederick, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Valentin Magidson

    Optical Microscopy and Analysis Laboratory, Frederick National Laboratory for Cancer Research, Frederick, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ryoichiro Kageyama

    Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Mark Lewandoski

    Genetics of Vertebrate Development Section, Cancer and Developmental Biology Lab, National Cancer Institute, National Institutes of Health, Frederick, United States
    For correspondence
    lewandom@mail.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1066-3735

Funding

National Cancer Institute (ZIA BC010338-19)

  • Mark Lewandoski

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

Ethics

Animal experimentation: Animal experimentation: All experimental procedures followed the National Institutes of Health Guidelines for animal care and use, and were approved by the NCI-Frederick Animal Care and Use Committee. (Animal Study Protocol 17-069)

Reviewing Editor

  1. Marianne E Bronner, California Institute of Technology, United States

Publication history

  1. Received: January 30, 2020
  2. Accepted: November 18, 2020
  3. Accepted Manuscript published: November 19, 2020 (version 1)
  4. Version of Record published: December 4, 2020 (version 2)
  5. Version of Record updated: January 18, 2021 (version 3)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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