Fine-tuning of Notch signaling sets the boundary of the organ of Corti and establishes sensory cell fates

  1. Martin L Basch
  2. Rogers M Brown
  3. Hsin-I Jen
  4. Fatih Semerci
  5. Frederic Depreux
  6. Renée Edlund
  7. Hongyuan Zhang
  8. Christine R Norton
  9. Thomas Gridley
  10. Susan E Cole
  11. Angelika Doetzlhofer
  12. Mirjana Maletic-Savatic
  13. Neil Segil
  14. Andrew K Groves  Is a corresponding author
  1. Case Western Reserve University, United States
  2. Baylor College of Medicine, United States
  3. Rosalind Franklin University of Medicine and Science, United States
  4. Maine Medical Center Research Institute, United States
  5. The Ohio State University, United States
  6. Johns Hopkins University, School of Medicine, United States
  7. Keck School of Medicine, University of Southern California, United States

Abstract

The signals that induce the organ of Corti and define its boundaries in the cochlea are poorly understood. We show that two Notch modifiers, Lfng and Mfng, are transiently expressed precisely at the neural boundary of the organ of Corti. Cre-Lox fate mapping shows this region gives rise to inner hair cells and their associated inner phalangeal cells. Mutation of Lfng and Mfng disrupts this boundary, producing unexpected duplications of inner hair cells and inner phalangeal cells. This phenotype is mimicked by other mouse mutants or pharmacological treatments that lower but not abolish Notch signaling. However, strong disruption of Notch signaling causes a very different result, generating many ectopic hair cells at the expense of inner phalangeal cells. Our results show that Notch signaling is finely calibrated in the cochlea to produce precisely tuned levels of signaling that first set the boundary of the organ of Corti and later regulate hair cell development.

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Author details

  1. Martin L Basch

    Department of Otolaryngology Head and Neck Surgery, University Hospitals, Case Medical Center, Case Western Reserve University, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Rogers M Brown

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Hsin-I Jen

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Fatih Semerci

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Frederic Depreux

    Department of Cell Biology and Anatomy, Rosalind Franklin University of Medicine and Science, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Renée Edlund

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Hongyuan Zhang

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Christine R Norton

    Maine Medical Center Research Institute, Scarborough, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Thomas Gridley

    Maine Medical Center Research Institute, Scarborough, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Susan E Cole

    Department of Molecular Genetics, The Ohio State University, Columbus, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Angelika Doetzlhofer

    Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Mirjana Maletic-Savatic

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Neil Segil

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Andrew K Groves

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    For correspondence
    akgroves@bcm.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0784-7998

Funding

National Institute on Deafness and Other Communication Disorders (NIH DC006185)

  • Andrew K Groves

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal experiments in this study were carried out in accordance with the Institutional Animal Care and Use Committee protocol (AN4956) at Baylor College of Medicine.

Copyright

© 2016, Basch 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. Martin L Basch
  2. Rogers M Brown
  3. Hsin-I Jen
  4. Fatih Semerci
  5. Frederic Depreux
  6. Renée Edlund
  7. Hongyuan Zhang
  8. Christine R Norton
  9. Thomas Gridley
  10. Susan E Cole
  11. Angelika Doetzlhofer
  12. Mirjana Maletic-Savatic
  13. Neil Segil
  14. Andrew K Groves
(2016)
Fine-tuning of Notch signaling sets the boundary of the organ of Corti and establishes sensory cell fates
eLife 5:e19921.
https://doi.org/10.7554/eLife.19921

Share this article

https://doi.org/10.7554/eLife.19921

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