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.
","abstract_html":"<p>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.</p>","abstract_has_math":false,"creators":["Kowalik, Lukasz"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":["A. James Hudspeth"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-01-01T08:00:00Z","date_published":"2010-01-01T08:00:00Z","updated_at":"2026-07-24T04:11:55Z","subjects":["sound frequency perception","hair cells","tonotopic gradient","DNER","PTP","hair-bundle formation","Life Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/268","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["A. James Hudspeth"]},{"key":"dc:creator","label":"Author","values":["Kowalik, Lukasz"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["sound frequency perception","hair cells","tonotopic gradient","DNER","PTP","hair-bundle formation","Life Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/268"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["Cellular Signaling in Development of the Cochlear Tonotopic Gradient"]}]}],"canonical_facts":{"dc:contributor":["A. James Hudspeth"],"dc:creator":["Kowalik, Lukasz"],"dc:description.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.
"],"dc:identifier":["https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/268"],"dc:subject":["sound frequency perception","hair cells","tonotopic gradient","DNER","PTP","hair-bundle formation","Life Sciences"],"dc:title":["Cellular Signaling in Development of the Cochlear Tonotopic Gradient"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T04:11:55Z"}