Student Theses and Dissertations

Title

Cellular Signaling in Development of the Cochlear Tonotopic Gradient

Date of Award

2010

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Hudspeth Laboratory

Abstract

The accurate perception of sound frequency by a vertebrate results from tuning of hair cells, which are arranged along the auditory organ according to their preferred frequencies. This arrangement is termed a tonotopic gradient. The tuning results from coordination of many cellular and extracellular features. Seeking the mechanisms that orchestrate those features and govern the tonotopic gradient, we used expression microarrays to identify genes differentially expressed between the high and low-frequency regions of the chick's cochlea and confirmed the results by qRTPCR. Of the three signaling pathways that were represented extensively in the results, we focused on the notch-delta pathway and particularly on DNER, a putative notch ligand, and PTP a receptor phosphatase that controls DNER trafficking. Immunolabeling revealed a polarized, mutually exclusive localization pattern for the two proteins. After using morpholinos to decrease the expression of DNER and PTP, as well as an retroviral vector to overexpress DNER, we observed disturbances of hair-bundle morphology and orientation. Our results suggest a role for DNER and PTP in hair-bundle formation and potentially specification of tonotopy.

Comments

A Thesis Presented to the Faculty of The Rockefeller University in Partial Ful llment of the Requirements for the degree of Doctor of Philosophy

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