Author ORCID Identifier

https://orcid.org/0000-0002-7482-0250

Year of Publication

2018

Degree Name

Master of Science (MS)

Document Type

Master's Thesis

College

Medicine

Department

Medical Sciences

First Advisor

Dr. Gregory I. Frolenkov

Abstract

Development of hair cell stereocilia bundles involves three stages: elongation, thickening, and supernumerary stereocilia retraction. Although Myo-XVa is known to be essential for stereocilia elongation, its role in retraction/thickening remains unknown. We quantified stereocilia numbers/diameters in shaker-2 mice (Myo15sh2) that have deficiencies in “long” and “short” isoforms of myosin-XVa, and in mice lacking only the “long” myosin-XVa isoform (Myo15ΔN). Our data showed that myosin-XVa is largely not involved in the developmental retraction of supernumerary stereocilia. In normal development, the diameters of the first (tallest)/second row stereocilia within a bundle are equal and grow simultaneously. The diameter of the third row stereocilia increases together with that of taller stereocilia until P1-2 and then either decreases almost two-fold in inner hair cells (IHCs) or stays the same in outer hair cells (OHCs), resulting in a prominent diameter gradation in IHCs and less prominent in OHCs. Sh2 mutation abolishes this gradation in IHCs/OHCs. Stereocilia of all rows grow in diameters nearly equally in Myo15sh2/sh2 IHCs and OHCs. Conversely, ΔN mutation does not affect normal stereocilia diameter gradation until ~P8. Therefore, myosin-XVa “short” isoform is essential for developmental thinning of third row stereocilia, which causes diameter gradation within a hair bundle.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2018.321

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