A gradient of Wnt activity positions the neurosensory domains of the inner ear

Abstract
Data availability
Article and author information
Metrics

Abstract

The auditory and vestibular organs of the inner ear and the neurons that innervate them originate from Sox2-positive and Notch-active neurosensory domains specified at early stages of otic development. Sox2 is initially present throughout the otic placode and otocyst, then it becomes progressively restricted to a ventro-medial domain. Using gain and loss-of-function approaches in the chicken otocyst, we show that these early changes in Sox2 expression are regulated in a dose-dependent manner by Wnt/beta-catenin signalling. Both high and very low levels of Wnt activity repress Sox2 and neurosensory competence. However, intermediate levels allow the maintenance of Sox2 expression and sensory organ formation. We propose that a dorso-ventral (high-to-low) gradient and wave of Wnt activity initiated at the dorsal rim of the otic placode progressively restricts Sox2 and Notch activity to the ventral half of the otocyst, thereby positioning the neurosensory competent domains in the inner ear.

Data availability

Source data files have been provided for the quantification of the Wnt reporter shown in Figure 1

Article and author information

Author details

Magdalena Żak

The Ear Institute, University College London, London, United Kingdom

For correspondence
m.zak@ucl.ac.uk

Competing interests
The authors declare that no competing interests exist.
Nicolas Daudet

The Ear Institute, University College London, London, United Kingdom

For correspondence
n.daudet@ucl.ac.uk

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-4039-4716

Funding

Medical Research Council (MR/S003029/1)

Magdalena Żak
Nicolas Daudet

Action on Hearing Loss (G76)

Magdalena Żak
Nicolas Daudet

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

Ethics

Animal experimentation: All experimental procedures on fertilized chicken eggs (2-8 days of incubation) were carried out in accordance with the United Kingdom Animals (Scientific Procedures) Act (ASPA) of 1986 and following the "3Rs" principles (Replacement, Reduction and Refinement) in conducting animal research. As per the ASPA 1986, the use of chicken embryos (Gallus Gallus) aged less than two third of the incubation period does not require formal approval and a Home Office Project Licence.

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.