Fine-tuning of Notch signaling sets the boundary of the organ of Corti and establishes sensory cell fates
- Case Western Reserve University, United States
- Baylor College of Medicine, United States
- Rosalind Franklin University of Medicine and Science, United States
- Maine Medical Center Research Institute, United States
- The Ohio State University, United States
- Johns Hopkins University, School of Medicine, United States
- 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.
Article and author information
Author details
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.
Reviewing Editor
- Tanya T Whitfield, University of Sheffield, United Kingdom
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.
Version history
- Received: July 22, 2016
- Accepted: December 12, 2016
- Accepted Manuscript published: December 14, 2016 (version 1)
- Version of Record published: January 4, 2017 (version 2)
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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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
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