Skip to main content

Umbrella menu

  • SfN.org
  • eNeuro
  • The Journal of Neuroscience
  • Neuronline
  • BrainFacts.org

Main menu

  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Collections
  • ALERTS
  • FOR AUTHORS
    • Preparing a Manuscript
    • Submission Guidelines
    • Fees
    • Journal Club
    • eLetters
    • Submit
  • EDITORIAL BOARD
  • ABOUT
    • Overview
    • Advertise
    • For the Media
    • Rights and Permissions
    • Privacy Policy
    • Feedback
  • SUBSCRIBE
  • SfN.org
  • eNeuro
  • The Journal of Neuroscience
  • Neuronline
  • BrainFacts.org

User menu

  • Log in
  • Subscribe
  • My alerts

Search

  • Advanced search
Journal of Neuroscience
  • Log in
  • Subscribe
  • My alerts
Journal of Neuroscience

Advanced Search

Submit a Manuscript
  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Collections
  • ALERTS
  • FOR AUTHORS
    • Preparing a Manuscript
    • Submission Guidelines
    • Fees
    • Journal Club
    • eLetters
    • Submit
  • EDITORIAL BOARD
  • ABOUT
    • Overview
    • Advertise
    • For the Media
    • Rights and Permissions
    • Privacy Policy
    • Feedback
  • SUBSCRIBE
PreviousNext
Cover ArticleResearch Articles, Development/Plasticity/Repair

The Notch Ligand Jagged1 Is Required for the Formation, Maintenance, and Survival of Hensen's Cells in the Mouse Cochlea

Elena Chrysostomou, Luyi Zhou, Yuanzhao L. Darcy, Kaley A. Graves, Angelika Doetzlhofer and Brandon C. Cox
Journal of Neuroscience 2 December 2020, 40 (49) 9401-9413; DOI: https://doi.org/10.1523/JNEUROSCI.1192-20.2020
Elena Chrysostomou
1Solomon H. Snyder Department of Neuroscience and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Luyi Zhou
3Departments of Pharmacology
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuanzhao L. Darcy
3Departments of Pharmacology
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kaley A. Graves
3Departments of Pharmacology
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Angelika Doetzlhofer
1Solomon H. Snyder Department of Neuroscience and
2Center for Hearing and Balance, Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brandon C. Cox
3Departments of Pharmacology
4Otolaryngology, Southern Illinois University School of Medicine, Springfield, Illinois 62702
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

During cochlear development, the Notch ligand JAGGED 1 (JAG1) plays an important role in the specification of the prosensory region, which gives rise to sound-sensing hair cells and neighboring supporting cells (SCs). While JAG1's expression is maintained in SCs through adulthood, the function of JAG1 in SC development is unknown. Here, we demonstrate that JAG1 is essential for the formation and maintenance of Hensen's cells, a highly specialized SC subtype located at the edge of the auditory epithelium. Using Sox2CreERT2/+::Jag1loxP/loxP mice of both genders, we show that Jag1 deletion at the onset of differentiation, at embryonic day 14.5, disrupted Hensen's cell formation. Similar loss of Hensen's cells was observed when Jag1 was deleted after Hensen's cell formation at postnatal day (P) 0/P1 and fate-mapping analysis revealed that in the absence of Jag1, some Hensen's cells die, but others convert into neighboring Claudius cells. In support of a role for JAG1 in cell survival, genes involved in mitochondrial function and protein synthesis were downregulated in the sensory epithelium of P0 cochlea lacking Jag1. Finally, using Fgfr3-iCreERT2::Jag1loxP/loxP mice to delete Jag1 at P0, we observed a similar loss of Hensen's cells and found that adult Jag1 mutant mice have hearing deficits at the low-frequency range.

SIGNIFICANCE STATEMENT Hensen's cells play an essential role in the development and homeostasis of the cochlea. Defects in the biophysical or functional properties of Hensen's cells have been linked to auditory dysfunction and hearing loss. Despite their importance, surprisingly little is known about the molecular mechanisms that guide their development. Morphologic and fate-mapping analyses in our study revealed that, in the absence of the Notch ligand JAGGED1, Hensen's cells died or converted into Claudius cells, which are specialized epithelium-like cells outside the sensory epithelium. Confirming a link between JAGGED1 and cell survival, transcriptional profiling showed that JAGGED1 maintains genes critical for mitochondrial function and tissue homeostasis. Finally, auditory phenotyping revealed that JAGGED1's function in supporting cells is necessary for low-frequency hearing.

  • Claudius cells
  • cochlea development
  • Hensen's cells
  • Jagged1
  • Notch
  • supporting cells

SfN exclusive license.

View Full Text

Member Log In

Log in using your username and password

Enter your Journal of Neuroscience username.
Enter the password that accompanies your username.
Forgot your user name or password?

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

Back to top

In this issue

The Journal of Neuroscience: 40 (49)
Journal of Neuroscience
Vol. 40, Issue 49
2 Dec 2020
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Advertising (PDF)
  • Ed Board (PDF)
Email

Thank you for sharing this Journal of Neuroscience article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
The Notch Ligand Jagged1 Is Required for the Formation, Maintenance, and Survival of Hensen's Cells in the Mouse Cochlea
(Your Name) has forwarded a page to you from Journal of Neuroscience
(Your Name) thought you would be interested in this article in Journal of Neuroscience.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
View Full Page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Citation Tools
The Notch Ligand Jagged1 Is Required for the Formation, Maintenance, and Survival of Hensen's Cells in the Mouse Cochlea
Elena Chrysostomou, Luyi Zhou, Yuanzhao L. Darcy, Kaley A. Graves, Angelika Doetzlhofer, Brandon C. Cox
Journal of Neuroscience 2 December 2020, 40 (49) 9401-9413; DOI: 10.1523/JNEUROSCI.1192-20.2020

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Respond to this article
Request Permissions
Share
The Notch Ligand Jagged1 Is Required for the Formation, Maintenance, and Survival of Hensen's Cells in the Mouse Cochlea
Elena Chrysostomou, Luyi Zhou, Yuanzhao L. Darcy, Kaley A. Graves, Angelika Doetzlhofer, Brandon C. Cox
Journal of Neuroscience 2 December 2020, 40 (49) 9401-9413; DOI: 10.1523/JNEUROSCI.1192-20.2020
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Keywords

  • Claudius cells
  • cochlea development
  • Hensen's cells
  • Jagged1
  • Notch
  • supporting cells

Responses to this article

Respond to this article

Jump to comment:

No eLetters have been published for this article.

Related Articles

Cited By...

More in this TOC Section

Research Articles

  • Prefrontal α7nAChR signaling differentially modulates afferent drive and trace fear conditioning behavior in adolescent and adult rats
  • Tuba activates Cdc42 during neuronal polarization downstream of the small GTPase Rab8a
  • Overlooked tertiary sulci serve as a meso-scale link between microstructural and functional properties of human lateral prefrontal cortex
Show more Research Articles

Development/Plasticity/Repair

  • PAK1 positively regulates oligodendrocyte morphology and myelination.
  • Brain-Derived Neurotrophic Factor/Tropomyosin Receptor Kinase B Signaling Controls Excitability and Long-Term Depression in Oval Nucleus of the BNST
  • Naturalistic Language Input is Associated with Resting-State Functional Connectivity in Infancy
Show more Development/Plasticity/Repair
  • Home
  • Alerts
  • Visit Society for Neuroscience on Facebook
  • Follow Society for Neuroscience on Twitter
  • Follow Society for Neuroscience on LinkedIn
  • Visit Society for Neuroscience on Youtube
  • Follow our RSS feeds

Content

  • Early Release
  • Current Issue
  • Issue Archive
  • Collections

Information

  • For Authors
  • For Advertisers
  • For the Media
  • For Subscribers

About

  • About the Journal
  • Editorial Board
  • Privacy Policy
  • Contact
  • Feedback
(JNeurosci logo)
(SfN logo)

Copyright © 2021 by the Society for Neuroscience.
JNeurosci Online ISSN: 1529-2401

The ideas and opinions expressed in JNeurosci do not necessarily reflect those of SfN or the JNeurosci Editorial Board. Publication of an advertisement or other product mention in JNeurosci should not be construed as an endorsement of the manufacturer’s claims. SfN does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of any material contained in JNeurosci.