Title: An analysis of the development of the cochlear-vestibular ganglion
Description: Unlike the organs of other sensory systems, the inner ear is partitioned to register two very different modalities: hearing and position sense. In the vestibular system, the accuracy of the neural connections allows the animal to distinguish motions of the head and identify the direction of gravity, whereas the tonotopic fidelity of the auditory projections allows the detection of single sound frequencies. Understanding auditory circuit assembly has been a significant challenge because of the small size and inaccessibility of the inner ear and difficulties labeling and imaging embryonic neurons. We used Cre-lox technology to visualize the morphological development of the auditory circuits from their origin in the otic vesicle to the formation of connections with their targets in the cochlea and in the cochlear nucleus. We found that auditory precursors are segregated from vestibular precursors early in neurogenesis. In contrast to previous reports, cochlear ganglion neurons with type I and type II morphologies are apparent before birth and develop within common pools of precursors. Cochlear ganglion axons are topographically organized in the auditory brainstem as early as e15.5, when the cochlear nucleus is still immature and before the maturation of the hair cells in the cochlea. These findings suggest intrinsic programs of differentiation that direct early auditory circuit assembly events before the maturation of presynaptic and postsynaptic target cells.

A human mutation in the GATA3 gene results in sensorineural deafness present at birth. The mouse mutant is early embryonic lethal, so the roles of GATA3 in auditory neurons remain unknown. It is hypothesized that GATA3 defines the cochlear ganglion fate and regulates the expression of those genes that specify cell fate and the formation of specific connections between the ear and the central auditory system. To test whether GATA3 is necessary for cochlear ganglion neuron development and function, GATA3 was deleted specifically in the cells of the developing cochlear ganglion using Cre-lox technology. Unfortunately this Cre-lox technology proved to be toxic to these cells; therefore the roles of GATA3 have continued to be elusive.