Elastic force restricts the growth of the murine utricle

Abstract
Data availability
Article and author information
Metrics

Abstract

Dysfunctions of hearing and balance are often irreversible in mammals owing to the inability of cells in the inner ear to proliferate and replace lost sensory receptors. To determine the molecular basis of this deficiency we have investigated the dynamics of growth and cellular proliferation in a murine vestibular organ, the utricle. Based on this analysis, we have created a theoretical model that captures the key features of the organ's morphogenesis. Our experimental data and model demonstrate that an elastic force opposes growth of the utricular sensory epithelium during development, confines cellular proliferation to the organ’s periphery, and eventually arrests its growth. We find that an increase in cellular density and the subsequent degradation of the transcriptional cofactor Yap underlie this process. A reduction in mechanical constraints results in accumulation and nuclear translocation of Yap, which triggers proliferation and restores the utricle's growth; interfering with Yap's activity reverses this effect.

Data availability

The following previously published data sets were used

1. Gnedeva K
2. Hudspeth AJ
(2015) Gene expression in the developing murine utricle
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE72293).

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72293

Article and author information

Author details

Ksenia Gnedeva

Laboratory of Sensory Neuroscience, Howard Hughes Medical Institute, The Rockefeller University, New York, United States

For correspondence
gnedeva@usc.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-3870-9256
Adrian Jacobo

Laboratory of Sensory Neuroscience, Howard Hughes Medical Institute, The Rockefeller University, New York, United States

Competing interests
The authors declare that no competing interests exist.
Joshua D Salvi

Laboratory of Sensory Neuroscience, Howard Hughes Medical Institute, The Rockefeller University, New York, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5140-7746
Aleksandra A Petelski

Laboratory of Sensory Neuroscience, Howard Hughes Medical Institute, The Rockefeller University, New York, United States

Competing interests
The authors declare that no competing interests exist.
A James Hudspeth

Laboratory of Sensory Neuroscience, Howard Hughes Medical Institute, The Rockefeller University, New York, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-0295-1323

Funding

Howard Hughes Medical Institute

A James Hudspeth

Robertson Therapeutic Development Fund

Ksenia Gnedeva
A James Hudspeth

National Institute on Deafness and Other Communication Disorders (2T32DC009975-07)

Ksenia Gnedeva

F. M. Kirby Foundation (DSG2000164)

Adrian Jacobo

National Institute on Deafness and Other Communication Disorders (F30DC013468)

Joshua D Salvi

National Institute of General Medical Sciences (T32GM007739)

Joshua D Salvi

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

Ethics

Animal experimentation: Experiments were conducted in accordance with the policies of The Rockefeller University's Institutional Animal Care and Use Committee (IACUC Protocol 15832) and the Keck School of Medicine of the University of Southern California (IACUC Protocol 20108).

Copyright

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.