Neural circuits must be precisely organized for sensory information from the outside world to be processed by the brain. In the auditory system, spiral ganglion neurons are the sole source of auditory input to the central nervous system. Functional spiral ganglion neurons are required for the best available treatment for sensorineural deafness, the cochlear implant. We used genetic fate mapping of the Neurogenin 1-positive neurogenic domain in the mouse otic vesicle to visualize the morphology of individual spiral ganglion neurons throughout development. We identified the timing of key features of spiral ganglion development. These included the segregation of auditory and vestibular precursors, the specification and development of the peripheral processes of Type I and Type II spiral ganglion neurons in the cochlea, and the topographic organization of central processes in the immature cochlear nucleus.
We then comprehensively analyzed spiral ganglion gene expression over the course of these developmental changes. We identified a cohort of signature genes specifically expressed in spiral ganglion neurons over the course of development. This cohort of genes included both genes previously known to be expressed in spiral ganglion neurons, and a number of exciting new genes that have not been examined in the auditory system. Therefore, this study provides a resource for the scientific community in general, and may inform the development of a number of potential treatments for hearing disorders.
We determined that the transcription factor GATA3 plays an ongoing role in maintaining spiral ganglion fate and regulating the timing of spiral ganglion development. Removing GATA3 after spiral ganglion specification resulted in the disorganization of processes extending in the inner ear but not the processes extending into the cochlear nucleus. While there was a partial de-repression of vestibular genes after losing GATA3, the majority of changes in gene expression changes indicated an acceleration of neuronal development. We hypothesize that similar to their roles in the immune system, GATA3, FOG proteins, and Maf factors dynamically interact to regulate the ongoing specification of spiral ganglion neurons, the timing of spiral ganglion differentiation, and spiral ganglion neuron circuit assembly in the cochlea.
|School Location:||United States -- Massachusetts|
|Source:||DAI-B 71/07, Dissertation Abstracts International|
|Subjects:||Audiology, Neurobiology, Developmental biology|
|Keywords:||Auditory neurons, Cochlea, GATA3, Microarrays, Spiral ganglion, Vestibular ganglion|
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