Timing of delamination of inner ear neurons specifies their topography and target innervation

Abstract

The neurons of the inner ear delaminate from a sensorineurogenic epithelium in the ventral part of the otocyst. Delaminated neuroblasts then condense to form the acoustico-vestibular ganglion (AVG). As they differentiate, the neurons connect mechanosensory hair cells (HCs) of the inner ear with their targets in the hindbrain in a precise topographical manner. However, it is unclear how or when positional identities of neurons are specified within the acoustico-vestibular ganglion (AVG), such that topographical information from HCs is maintained into the auditory centres of the brain. Here we find that the time of delamination from the otocyst correlates with neuroblast position in the ganglion. Using markers for neuronal differentiation, we find that the ganglion differentiates from a proximal to distal wave. Neurons that differentiate first innervate the vestibular apparatus, including the lagena and the proximal regions of the BP. Using sequential somatic cell labelling, we find that the central projection also follows a similar dependency on delamination order. Our studies show that the time of delamination of otic neuroblasts presage their target innervation choice and fibre positions within the developing eighth cranial nerve. We suggest that temporal information specifies the spatial identities during early inner ear neuron development.