Gene Expression During Postnatal Development of the Central Auditory Pathway

Vanderbilt University, Nashville TN

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Abstract

DESCRIPTION (provided by applicant): A comprehensive understanding of the genetic and environmental factors that govern pre- and postnatal development of the auditory system is essential for conceiving of and improving existing therapeutic approaches that address impaired auditory function in clinical populations. Since their influence varies between individuals and by etiology, these factors combine to shape auditory processing in different ways. As a tool for revealing the underlying structure of the auditory system, and how it develops and changes with experience, studies of gene expression are indispensable. Some of these genes govern general metabolic and regulatory functions common to all central nervous system structures. Others are linked to specific processes, such as cell communication, motility, fate and differentiation. Moreover, their expression varies by age, between regions of the brain, and with sensory experience. To date, comprehensive gene expression profiles have not been generated for most structures in the central auditory pathway, and none are complete for any species at any age. The scientific aims of this proposal address this need in a novel study designed to document changes in gene and protein expression in the mouse at key stages of postnatal development to maturity. The PI is an established auditory neuroscientist whose research program combines neuroanatomical and neurophysiological methods to link structure and function in auditory and multisensory circuits in the brain. In terms of career development, the purpose of this proposal is to expand and enrich the scope of this research program by equipping the PI with the tools of molecular biology. Under the supervision of an expert mentor, the PI will be trained to characterize gene expression in selected brain areas, and then follow up by localizing transcripts to those brain structures at the mRNA and protein levels. Retooling in this manner will enable the PI to plan and conduct studies that are informed by the transcriptome profile of specific brain regions. Compared to existing strategies, the whole genome expression profiling approach is more comprehensive in scope and more effectively bridges structure and function. The scientific and career development goals of this K18 proposal will be achieved in the context of a study that combines DNA microarray analysis, in situ hybridization, and immunohistochemistry to: (1) identify genes that are differentially expressed in auditory cortex, medial geniculate, and inferior colliculus during postnatal development; and (2) localize the transcripts of selected genes to their expression within the cells, divisions, and laminae of each structure. These efforts will generate the first catalog of gene expression in the mouse central auditory pathway at key stages of postnatal development, while adding an important new dimension to studies of brain structure and function by the PI. Overall, this proposal advances efforts to characterize key neurobiological processes associated with communication disorders, such as hearing loss, autism, and stroke.