title: Sox2 and JAGGED1 expression in normal and drug-damaged adult mouse inner ear.
abstract: Inner ear hair cells detect environmental signals associated with hearing, balance, and body orientation. In humans and other mammals, significant hair cell loss leads to irreversible hearing and balance deficits, whereas hair cell loss in nonmammalian vertebrates is repaired by the spontaneous generation of replacement hair cells. Research in mammalian hair cell regeneration is hampered by the lack of in vivo damage models for the adult mouse inner ear and the paucity of cell-type-specific markers for non-sensory cells within the sensory receptor epithelia. The present study delineates a protocol to drug damage the adult mouse auditory epithelium (organ of Corti) in situ and uses this protocol to investigate Sox2 and Jagged1 expression in damaged inner ear sensory epithelia. In other tissues, the transcription factor Sox2 and a ligand member of the Notch signaling pathway, Jagged1, are involved in regenerative processes. Both are involved in early inner ear development and are expressed in developing support cells, but little is known about their expressions in the adult. We describe a nonsurgical technique for inducing hair cell damage in adult mouse organ of Corti by a single high-dose injection of the aminoglycoside kanamycin followed by a single injection of the loop diuretic furosemide. This drug combination causes the rapid death of outer hair cells throughout the cochlea. Using immunocytochemical techniques, Sox2 is shown to be expressed specifically in support cells in normal adult mouse inner ear and is not affected by drug damage. Sox2 is absent from auditory hair cells, but is expressed in a subset of vestibular hair cells. Double-labeling experiments with Sox2 and calbindin suggest Sox2-positive hair cells are Type II. Jagged1 is also expressed in support cells in the adult ear and is not affected by drug damage. Sox2 and Jagged1 may be involved in the maintenance of support cells in adult mouse inner ear.
authors.affiliation: Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology-Head and Neck Surgery, University of Washington, CHDD CD176, Box 357923, Seattle, WA 98195-7923, USA. oesterle@u.washington.edu
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Oesterle
authors.forename: Sean
authors.initials: S
authors.lastname: Campbell
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Taylor
authors.forename: Andrew
authors.initials: A
authors.lastname: Forge
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Hume
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000633:toxicity; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002645:Chickens; D015834:Cochlear Diseases / Q000139:chemically induced; D004195:Disease Models, Animal; D004232:Diuretics / Q000633:toxicity; D005665:Furosemide / Q000633:toxicity; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D000072100:Jagged-1 Protein; D007612:Kanamycin / Q000633:toxicity; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D009925:Organ of Corti / Q000187:drug effects / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D004232:Diuretics; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D055748:SOXB1 Transcription Factors; D000072099:Serrate-Jagged Proteins; C527783:Sox2 protein, mouse; D007612:Kanamycin; D005665:Furosemide