A gradient in glucose metabolism regulates hair cell morphology along the tonotopic axis of the developing cochlea

Abstract

AbstractIn vertebrates with elongated auditory organs, mechanosensory hair cells (HCs) are organised such that complex sounds are broken down into their component frequencies along the basal-to-apical 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 glucose catabolism, alters normal Bmp7 and Chordin like-1 signalling leading to flattening of tonotopic patterning and hair cell morphology along the axis. These findings indicate a causal link between morphogen signalling and metabolic reprogramming in specifying tonotopic morphologies in developing auditory HCs.