Gradients of Glucose Metabolism Regulate Morphogen Signalling Required for Specifying Tonotopic Organisation in the Chicken Cochlea

Overview

Journal Elife

Specialty Biology

Date 2023 Aug 4

PMID 37539863

Authors

James D B OSullivan

Thomas S Blacker

Claire Scott

Weise Chang

Mohi Ahmed

Val Yianni

Zoe F Mann

Affiliations

Soon will be listed here.

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, 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 microscopy, 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 HC 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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