title: A search for factors specifying tonotopy implicates DNER in hair-cell development in the chick's cochlea.
abstract: The accurate perception of sound frequency by vertebrates relies upon the tuning of hair cells, which are arranged along auditory organs according to frequency. This arrangement, which is termed a tonotopic gradient, results from the 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 cochlear regions of the chick (Gallus gallus). Of the three signaling systems that were represented extensively in the results, we focused on the notch pathway and particularly on DNER, a putative notch ligand, and PTPζ, a receptor phosphatase that controls DNER trafficking. Immunohistochemistry confirmed that both proteins are expressed more strongly in hair cells at the cochlear apex than in those at the base. At the apical surface of each hair cell, the proteins display polarized, mutually exclusive localization patterns. Using morpholinos to decrease the expression of DNER or PTPζ as well as a retroviral vector to overexpress DNER, we observed disturbances of hair-bundle morphology and orientation. Our results suggest a role for DNER and PTPζ in hair-cell development and possibly in the specification of tonotopy.
authors.affiliation: Howard Hughes Medical Institute and Laboratory of Sensory Neuroscience, Campus Box 314, The Rockefeller University, 1230 York Avenue, New York, NY 10065-6399, USA.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kowalik
authors.forename: A J
authors.initials: AJ
authors.lastname: Hudspeth
mesh_terms: D000818:Animals; D001307:Auditory Perception / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D002642:Chick Embryo; D003051:Cochlea / Q000166:cytology / Q000196:embryology*; D006198:Hair Cells, Auditory / Q000166:cytology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5