Expression of Oncomodulin in the Inner Ear 

Mitch Otu and Dwayne Simmons

Department of Otolaryngology, Washington University School of Medicine

In neurons and sensory cells, calcium plays a major role in signal transduction, acting as second messengers that regulate a variety of cellular processes essential for cellular function. Calcium-binding proteins (CBPs) play a significant role in those cellular processes since they regulate calcium levels by binding free calcium ions.  In the inner ear, calcium is known to play significant roles in hearing and balance function. The stereocilia of hair cells are bent by sound waves, which permits calcium ions to enter the hair cell. Those calcium ions may cause hair cells to release neurotransmitters onto ganglion nerve cells, causing efferent (brainstem) modulation of sensory input and thereby giving rise to our sense of hearing and balance. Unlike the other CBPs found in the mammalian organ of Corti such as calbindin, calmodulin and calretinin, beta parvalbumin (oncomodulin) has only been found in a subtype of auditory hair cells, the outer hair cell.  The active movement of outer hair cells in response to sounds is modulated by efferent nerves. The role of oncomodulin has thus been linked to efferent innervation. The purpose of this study was 1) to investigate whether oncomodulin is found in other hair cells during development and 2) to investigate the relationship between efferent innervation and the presence of oncomodulin.

The expression of oncomodulin was studied in the cochlea and vestibular organs of newborn rats. Earlier studies show oncomodulin is present in the cochlear outer hair cells beginning between postnatal day (P) 2 and P4. Using immunocytochemistry and RT-PCR, we find oncomodulin present in vestibular hair cells before cochlear hair cells. In vestibular regions, oncomodulin is expressed at P0 and P2 and is probably expressed at least in late embryonic stages. In vestibular organs, oncomodulin is found in a subtype of hair cells that are restricted to the striolar region, which is an important zone of reverse polarity. Within the striola, about half of the hair cells express oncomodulin. Vestibular organs have two types of hair cells: type I and type II hair cells. In combination with other concurrent studies, it appears that oncomodulin labels type I hair cells. In the loop-tail mouse mutant, the striolar region appears to be absent. We tested whether this was indeed true by labeling loop-tail vestibular organs for oncomodulin. In the mutant, we observe a band of vestibular hair cells that express oncomodulin similar to what is observed in normal animals. We did not find any specific relation between hair cells that express oncomodulin and efferent innervation. We used antibodies directed against vesicular acetylcholine transferase (anti-VAT) to label efferent nerve terminals in the inner ear. The anti-VAT labeling suggests that efferent terminals form calyceal endings on hair cells that are positive and negative for oncomodulin as early as P0. This is the first report of an extensive efferent innervation of vestibular sensory organs at birth. In conclusion, our results suggest that oncomodulin uniquely identifies a subset of striolar vestibular hair cells and that oncomodulin is expressed in vestibular hair cells before cochlear hair cells.