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  • Title: Jagged1-mediated Notch signaling regulates mammalian inner ear development independent of lateral inhibition.
    Author: Hao J, Koesters R, Bouchard M, Gridley T, Pfannenstiel S, Plinkert PK, Zhang L, Praetorius M.
    Journal: Acta Otolaryngol; 2012 Oct; 132(10):1028-35. PubMed ID: 22998557.
    Abstract:
    CONCLUSION: Jagged1-mediated Notch signaling regulates hair cell (HC) production in a distinct way rather than lateral inhibition mediated by Hes1 and Hes5. Jagged1 may interact with Notch3, probably via candidate downstream mediators Hesr1 and Hesr2, regulating the prosensory formation in the early stage. OBJECTIVES: To explore the function of the Jagged1-mediated Notch signaling pathway in mammalian inner ear development and its possible mechanism. METHODS: Using conditional gene targeting, a novel Jagged1 conditional knockout (Jag1-cko), Pax8(cre/+); Jag1(flox/flox), was established. The auditory brainstem response and swim ability test were utilized to identify functional disability. The expression of Jagged1, Notch3, Hes1, Hesr1, and Hesr2 was detected by immunofluorescence and immunohistochemistry. RESULTS: Our Jag1-cko model was established and survived well. It presented hearing impairment and balance disturbance with 'waltzing' behavior. Cochleae and vestibular apparatus were all found in our Jag1-cko model. Patch deficiency of outer hair cells (OHCs) was found on the apical and middle turns of the auditory epithelium. OHCs were totally missing on the basal turn. The stereociliary bundles were disorientated on the cristae. Unlike Hes1, no expression of Notch3, Hesr1, and Hesr2 was found on embryonic day 13.5 of the Jag1-cko model.
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