Gradients of glucose metabolism regulate morphogen signalling required for specifying tonotopic organization in the chicken cochlea

  1. James DB O'Sullivan
  2. Thomas S Blacker
  3. Claire Scott
  4. Weise Chang
  5. Mohi Ahmed
  6. Val Yianni
  7. Zoe F Mann  Is a corresponding author
  1. King's College London, United Kingdom
  2. University College London, United Kingdom
  3. National Institute on Deafness and Other Communication Disorders, United States

Abstract

In vertebrates with elongated auditory organs, mechanosensory hair cells (HCs) are organised such that complex sounds are broken down into their component frequencies along a proximal-to-distal long (tonotopic) axis. Acquisition of unique morphologies at the appropriate position along the chick cochlea, the basilar papilla (BP), requires that nascent HCs determine their tonotopic positions during development. The complex signalling within the auditory organ between a developing HC and its local niche along the cochlea is poorly understood. Using a combination of live imaging and NAD(P)H fluorescence lifetime imaging (FLIM) we reveal that there is a gradient in the cellular balance between glycolysis and the pentose phosphate pathway in developing HCs along the tonotopic axis. Perturbing this balance by inhibiting different branches of cytosolic glucose catabolism disrupts developmental morphogen signalling and abolishes the normal tonotopic gradient in hair cell morphology. These findings highlight a causal link between graded morphogen signalling and metabolic reprogramming in specifying the tonotopic identity of developing HCs.

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Author details

  1. James DB O'Sullivan

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Thomas S Blacker

    Research Department of Structural and Molecular Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8949-6238
  3. Claire Scott

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Weise Chang

    National Institute on Deafness and Other Communication Disorders, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Mohi Ahmed

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Val Yianni

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9857-7577
  7. Zoe F Mann

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    For correspondence
    zoe.mann@kcl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4916-9574

Funding

Biotechnology and Biological Sciences Research Council (BB/V006371/1)

  • Zoe F Mann

Physiological Society

  • Zoe F Mann

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

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. James DB O'Sullivan
  2. Thomas S Blacker
  3. Claire Scott
  4. Weise Chang
  5. Mohi Ahmed
  6. Val Yianni
  7. Zoe F Mann
(2023)
Gradients of glucose metabolism regulate morphogen signalling required for specifying tonotopic organization in the chicken cochlea
eLife 12:e86233.
https://doi.org/10.7554/eLife.86233

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https://doi.org/10.7554/eLife.86233