Genetic Dissection of Auditory Circuit Assembly

The goal of this project is to understand how auditory neurons acquire the unique properties that are essential for the perception of sound.  Currently, we are focused on the identification and analysis of genes that are expressed in auditory neurons, but not in the closely related vestibular ganglion neurons.  We are performing a large scale comparison of gene expression in purified populations of auditory and vestibular ganglion neurons.  In addition, we have initiated detailed studies of one auditory-specific transcription factor, GATA3, which is mutated in the human syndrome Hypoparathyrodisim, sensorineural Deafness, and Renal disease (HDR).  Loss of GATA3 from spiral ganglion neurons results in disorganized wiring of the cochlea, followed by apoptosis of mutant neurons.  As a result, GATA3 conditional mutant mice exhibit severe hearing impairment.  As well as elucidating the cellular basis of the observed wiring defect, we are using microarrays to identify putative GATA3 target genes.  Together, these studies will provide insights into the molecular mechanisms that guide assembly of the highly specific and precise neural circuits that connect the ear to the brain. The goal of this project is to understand how auditory neurons acquire the unique properties that are essential for the perception of sound.  Currently, we are focused on the identification and analysis of genes that are expressed in auditory neurons, but not in the closely related vestibular ganglion neurons.  We are performing a large scale comparison of gene expression in purified populations of auditory and vestibular ganglion neurons.  In addition, we have initiated detailed studies of one auditory-specific transcription factor, GATA3, which is mutated in the human syndrome Hypoparathyrodisim, sensorineural Deafness, and Renal disease (HDR).  Loss of GATA3 from spiral ganglion neurons results in disorganized wiring of the cochlea, followed by apoptosis of mutant neurons.  As a result, GATA3 conditional mutant mice exhibit severe hearing impairment.  As well as elucidating the cellular basis of the observed wiring defect, we are using microarrays to identify putative GATA3 target genes.  Together, these studies will provide insights into the molecular mechanisms that guide assembly of the highly specific and precise neural circuits that connect the ear to the brain.