Gradients of glucose metabolism regulate morphogen signalling required for specifying tonotopic organization in the chicken cochlea
- King's College London, United Kingdom
- University College London, United Kingdom
- 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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All data and source data are available in manuscript and supporting files.
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Author details
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.
Reviewing Editor
- Doris K Wu, National Institutes of Health, United States
Version history
- Preprint posted: April 11, 2022 (view preprint)
- Received: January 17, 2023
- Accepted: August 3, 2023
- Accepted Manuscript published: August 4, 2023 (version 1)
- Version of Record published: August 14, 2023 (version 2)
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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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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