Development and Maturation

Although the ear appears quite normal at the onset of hearing, the acquisition of sound transduction in the ear represents a massive molecular remodeling of sensory cells, neurons and their synaptic connections. Early studies in our laboratory focused on the advent of BK-type potassium channels in hair cells, as this is a key event in the onset of hearing, transforming immature spiking hair cells to those capable of encoding high frequency sounds. In these studies we identified major splice variants that govern the expression of these channels, but the molecular mechanisms linking channel expression and hearing sensitivity remain unknown. In collaboration with Dr. Sally Camper, we began exploring the role of thyroid hormone in hearing maturation. Congenital hypothyroidism leads to deafness and the critical window for thyroid hormone activity is at the onset of hearing. BK channel activity, among many other processes, is tightly connected to action of thyroid hormone. Below, we highlight one of our active projects in this area:

Thyroid Hormone and the Acquisition of Hearing in Normal and Regenerating Avian Ears

Thyroid hormone is essential to the maturation of hearing but identification of hormone-sensitive processes in hair cells is confounded by pleiotropic effects in the cochlea and elsewhere. Capitalizing on our previous work in the avian ear, which is capable of spontaneous hair cell regeneration, we are embarking on a new line of research examining the role of thyroid hormone in the regenerating ear. Using the goitrogen methimazole, we have developed methods to reduce total T3 levels by 90% in the embryonic chick ear and in posthatch animals. We have also established methods to eliminate 99% of the sensory hair cells in the chick cochlea using repeated doses of streptomycin. Preliminary experiments in embryos support the requirement for thyroid hormone in the maturation of hearing in chicks. Recent data also supports the hypothesis that thyroid hormone is essential to the regenerating ear.  These approaches will provide new insights into the factors that control hair cell maturation and may impact our approach to mammalian hair cell regeneration.