Crosstalk between glucose metabolism and morphogen signalling specifies tonotopic identity in developing hair cells.

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 the proximal-to-distal long (tonotopic) axis. Acquisition of frequency-specific morphologies at the appropriate positions 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 the developing HC and its local niche along the axis is currently poorly understood. Here we apply NAD(P)H fluorescence lifetime imaging (FLIM) to reveal metabolic gradients along the tonotopic axis of the developing BP. Re-shaping these gradients during development, by inhibiting different branch points of cytosolic glucose catabolism, alters normal morphogen signalling and abolishes tonotopic patterning, normalising the graded differences in hair cell morphology along the BP. These findings highlight a causal link between morphogen signalling and metabolic reprogramming in specifying tonotopic identity in developing auditory HCs.