Hair cell development in the mouse embryo

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): It has been estimated that one out of every thousand children is born with significant hearing and/or balance impairment. A substantial portion of these congenital disorders are sensorineural in origin, arising either within the sensory hair cells of the inner ear or within the brain regions to which the hair-cell signals project. Approximately 12 hair-cell genes have been identified that cause auditory and vestibular deficits. Despite these recent advances in the genetics of hearing loss, there has been little progress toward understanding the pathophysiology of congenital hearing and balance dysfunction. An obvious prerequisite to understanding these prenatal disorders is knowledge of how hair cells develop in the normal state. Toward that goal, the studies proposed here aim to advance an understanding of hair-cell development by examining the normal physiology of hair cells from prenatal mice. The project has two main objectives. The first aim is to characterize the prenatal acquisition of voltage sensitive conductances in vestibular hair cells. The second aim is to characterize the acquisition of mechanotransduction and adaptation in developing hair cells. Both of these aims will be addressed using the whole-cell, tight-seal technique to record from embryonic hair cells of the intact sensory epithelium (embryonic day 13 to birth). Mechanotransduction will be evoked by deflecting the hair bundles with either a stiff probe or a jet of fluid. A parallel molecular investigation will correlate the prenatal expression patterns of ion channel subunits and adaptation-associated proteins with the physiologic data. Ultimately, the objective is to understand how and when hair cells begin to function as hair cells. It is also expected that this work will provide a developmental timeline that may serve as reference for projects aimed at promoting hair cell regeneration.