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/School/Program

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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