1. Developmental Biology
  2. Neuroscience
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Cochlear progenitor number is controlled through mesenchymal FGF receptor signaling

  1. Sung-Ho Huh
  2. Mark E Warchol
  3. David M Ornitz  Is a corresponding author
  1. Washington University School of Medicine, United States
Research Article
  • Cited 35
  • Views 1,865
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Cite this article as: eLife 2015;4:e05921 doi: 10.7554/eLife.05921

Abstract

The sensory and supporting cells of the organ of Corti are derived from a limited number of progenitors. The mechanisms that regulate the number of sensory progenitors are not known. Here, we show that Fibroblast Growth Factors (FGF) 9 and 20, which are expressed in the non-sensory (Fgf9) and sensory (Fgf20) epithelium during otic development, regulate the number of cochlear progenitors. We further demonstrate that Fgf receptor (Fgfr) 1 signaling within the developing sensory epithelium is required for the differentiation of outer hair cells and supporting cells, while mesenchymal FGFRs regulate the size of the sensory progenitor population and the overall cochlear length. In addition, ectopic FGFR activation in mesenchyme was sufficient to increase sensory progenitor proliferation and cochlear length. These data define a feedback mechanism, originating from epithelial FGF ligands and mediated through periotic mesenchyme that controls the number of sensory progenitors and the length of the cochlea.

Article and author information

Author details

  1. Sung-Ho Huh

    Departments of Developmental Biology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Mark E Warchol

    Departments of Otolaryngology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. David M Ornitz

    Departments of Developmental Biology, Washington University School of Medicine, St Louis, United States
    For correspondence
    dornitz@wustl.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was carried out in strict accordance with the recommendations in the Guide for the Careand Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by theWashington University Division of Comparative Medicine Animal Studies Committee (Protocol Number20130201). All efforts were made to minimize animal suffering.

Reviewing Editor

  1. Tanya T Whitfield, University of Sheffield, United Kingdom

Publication history

  1. Received: December 5, 2014
  2. Accepted: April 25, 2015
  3. Accepted Manuscript published: April 27, 2015 (version 1)
  4. Version of Record published: May 18, 2015 (version 2)

Copyright

© 2015, Huh 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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