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

  1. Magdalena Żak  Is a corresponding author
  2. Nicolas Daudet  Is a corresponding author
  1. University College London, United Kingdom


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

  1. Magdalena Żak

    The Ear Institute, University College London, London, United Kingdom
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
  2. Nicolas Daudet

    The Ear Institute, University College London, London, United Kingdom
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4039-4716


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.


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.

Reviewing Editor

  1. Doris K Wu, NIDCD, NIH, United States

Version history

  1. Received: June 1, 2020
  2. Accepted: March 9, 2021
  3. Accepted Manuscript published: March 11, 2021 (version 1)
  4. Version of Record published: March 24, 2021 (version 2)
  5. Version of Record updated: April 1, 2021 (version 3)


© 2021, Żak & Daudet

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.


  • 1,213
    Page views
  • 157
  • 6

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Magdalena Żak
  2. Nicolas Daudet
A gradient of Wnt activity positions the neurosensory domains of the inner ear
eLife 10:e59540.

Further reading

    1. Developmental Biology
    2. Neuroscience
    Igor Y Iskusnykh, Nikolai Fattakhov ... Victor V Chizhikov
    Research Article

    Development of the nervous system depends on signaling centers – specialized cellular populations that produce secreted molecules to regulate neurogenesis in the neighboring neuroepithelium. In some cases, signaling center cells also differentiate to produce key types of neurons. The formation of a signaling center involves its induction, the maintenance of expression of its secreted molecules, and cell differentiation and migration events. How these distinct processes are coordinated during signaling center development remains unknown. By performing studies in mice, we show that Lmx1a acts as a master regulator to orchestrate the formation and function of the cortical hem (CH), a critical signaling center that controls hippocampus development. Lmx1a co-regulates CH induction, its Wnt signaling, and the differentiation and migration of CH-derived Cajal–Retzius neurons. Combining RNAseq, genetic, and rescue experiments, we identified major downstream genes that mediate distinct Lmx1a-dependent processes. Our work revealed that signaling centers in the mammalian brain employ master regulatory genes and established a framework for analyzing signaling center development.

    1. Developmental Biology
    2. Evolutionary Biology
    Salvatore D'Aniello, Stephanie Bertrand, Hector Escriva
    Feature Article

    Cephalochordates and tunicates represent the only two groups of invertebrate chordates, and extant cephalochordates – commonly known as amphioxus or lancelets – are considered the best proxy for the chordate ancestor, from which they split around 520 million years ago. Amphioxus has been an important organism in the fields of zoology and embryology since the 18th century, and the morphological and genomic simplicity of cephalochordates (compared to vertebrates) makes amphioxus an attractive model for studying chordate biology at the cellular and molecular levels. Here we describe the life cycle of amphioxus, and discuss the natural histories and habitats of the different species of amphioxus. We also describe their use as laboratory animal models, and discuss the techniques that have been developed to study different aspects of amphioxus.